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1. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

2. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

3. Comprehensive Fragment Screening of the SARS‐CoV‐2 Proteome Explores Novel Chemical Space for Drug Development

Author: Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Korn, Sophie Marianne, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J. J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, Silva Almeida, Marcius da, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes‐Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus‐Antunes, Nathane, Mompeán, Miguel, Cristtina Neves‐Martins, Thais, Ninot‐Pedrosa, Martí, Pinheiro, Anderson S., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel Á., Tsika, Aikaterini C., Almeida, Fabio C. L., Bax, Ad, Henzler‐Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt‐Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer‐Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Published: 2024

4. Systematic identification of structure-specific protein–protein interactions

Author: Holfeld, Aleš; https://orcid.org/0000-0003-0775-8634, Schuster, Dina; https://orcid.org/0000-0001-6611-8237, Sesterhenn, Fabian; https://orcid.org/0000-0001-8331-4344, Gillingham, Alison K; https://orcid.org/0009-0000-3835-2333, Stalder, Patrick; https://orcid.org/0000-0003-4005-8488, Haenseler, Walther; https://orcid.org/0000-0003-4868-3704, Barrio-Hernandez, Inigo; https://orcid.org/0000-0002-5686-0451, Ghosh, Dhiman; https://orcid.org/0000-0003-2087-8075, Vowles, Jane; https://orcid.org/0000-0002-7000-1581, Cowley, Sally A; https://orcid.org/0000-0003-0297-6675, Nagel, Luise; https://orcid.org/0000-0001-8844-7234, Khanppnavar, Basavraj; https://orcid.org/0000-0002-6637-3550, Serdiuk, Tetiana, Beltrao, Pedro; https://orcid.org/0000-0002-2724-7703, Korkhov, Volodymyr M; https://orcid.org/0000-0002-0962-9433, Munro, Sean; https://orcid.org/0000-0001-6160-5773, Riek, Roland; https://orcid.org/0000-0002-6333-066X, de Souza, Natalie; https://orcid.org/0000-0003-4286-8951, Picotti, Paola; https://orcid.org/0000-0002-4109-3552, Holfeld, Aleš; https://orcid.org/0000-0003-0775-8634, Schuster, Dina; https://orcid.org/0000-0001-6611-8237, Sesterhenn, Fabian; https://orcid.org/0000-0001-8331-4344, Gillingham, Alison K; https://orcid.org/0009-0000-3835-2333, Stalder, Patrick; https://orcid.org/0000-0003-4005-8488, Haenseler, Walther; https://orcid.org/0000-0003-4868-3704, Barrio-Hernandez, Inigo; https://orcid.org/0000-0002-5686-0451, Ghosh, Dhiman; https://orcid.org/0000-0003-2087-8075, Vowles, Jane; https://orcid.org/0000-0002-7000-1581, Cowley, Sally A; https://orcid.org/0000-0003-0297-6675, Nagel, Luise; https://orcid.org/0000-0001-8844-7234, Khanppnavar, Basavraj; https://orcid.org/0000-0002-6637-3550, Serdiuk, Tetiana, Beltrao, Pedro; https://orcid.org/0000-0002-2724-7703, Korkhov, Volodymyr M; https://orcid.org/0000-0002-0962-9433, Munro, Sean; https://orcid.org/0000-0001-6160-5773, Riek, Roland; https://orcid.org/0000-0002-6333-066X, de Souza, Natalie; https://orcid.org/0000-0003-4286-8951, and Picotti, Paola; https://orcid.org/0000-0002-4109-3552
Abstract: The physical interactome of a protein can be altered upon perturbation, modulating cell physiology and contributing to disease. Identifying interactome differences of normal and disease states of proteins could help understand disease mechanisms, but current methods do not pinpoint structure-specific PPIs and interaction interfaces proteome-wide. We used limited proteolysis–mass spectrometry (LiP–MS) to screen for structure-specific PPIs by probing for protease susceptibility changes of proteins in cellular extracts upon treatment with specific structural states of a protein. We first demonstrated that LiP–MS detects well-characterized PPIs, including antibody–target protein interactions and interactions with membrane proteins, and that it pinpoints interfaces, including epitopes. We then applied the approach to study conformation-specific interactors of the Parkinson’s disease hallmark protein alpha-synuclein (aSyn). We identified known interactors of aSyn monomer and amyloid fibrils and provide a resource of novel putative conformation-specific aSyn interactors for validation in further studies. We also used our approach on GDP- and GTP-bound forms of two Rab GTPases, showing detection of differential candidate interactors of conformationally similar proteins. This approach is applicable to screen for structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound protein states.
Published: 2024

5. Systematic identification of structure-specific protein–protein interactions

Author: Holfeld, Aleš; https://orcid.org/0000-0003-0775-8634, Schuster, Dina; https://orcid.org/0000-0001-6611-8237, Sesterhenn, Fabian; https://orcid.org/0000-0001-8331-4344, Stalder, Patrick; https://orcid.org/0000-0003-4005-8488, Haenseler, Walther; https://orcid.org/0000-0003-4868-3704, Barrio-Hernandez, Inigo; https://orcid.org/0000-0002-5686-0451, Ghosh, Dhiman, Vowles, Jane; https://orcid.org/0000-0002-7000-1581, Cowley, Sally A; https://orcid.org/0000-0003-0297-6675, Nagel, Luise; https://orcid.org/0000-0001-8844-7234, Khanppnavar, Basavraj; https://orcid.org/0000-0002-6637-3550, Beltrao, Pedro; https://orcid.org/0000-0002-2724-7703, Korkhov, Volodymyr M; https://orcid.org/0000-0002-0962-9433, Riek, Roland; https://orcid.org/0000-0002-6333-066X, de Souza, Natalie; https://orcid.org/0000-0003-4286-8951, Picotti, Paola; https://orcid.org/0000-0002-4109-3552, Holfeld, Aleš; https://orcid.org/0000-0003-0775-8634, Schuster, Dina; https://orcid.org/0000-0001-6611-8237, Sesterhenn, Fabian; https://orcid.org/0000-0001-8331-4344, Stalder, Patrick; https://orcid.org/0000-0003-4005-8488, Haenseler, Walther; https://orcid.org/0000-0003-4868-3704, Barrio-Hernandez, Inigo; https://orcid.org/0000-0002-5686-0451, Ghosh, Dhiman, Vowles, Jane; https://orcid.org/0000-0002-7000-1581, Cowley, Sally A; https://orcid.org/0000-0003-0297-6675, Nagel, Luise; https://orcid.org/0000-0001-8844-7234, Khanppnavar, Basavraj; https://orcid.org/0000-0002-6637-3550, Beltrao, Pedro; https://orcid.org/0000-0002-2724-7703, Korkhov, Volodymyr M; https://orcid.org/0000-0002-0962-9433, Riek, Roland; https://orcid.org/0000-0002-6333-066X, de Souza, Natalie; https://orcid.org/0000-0003-4286-8951, and Picotti, Paola; https://orcid.org/0000-0002-4109-3552
Abstract: Protein–protein interactions (PPIs) mediate numerous essential functions and regulatory events in living organisms. The physical interactome of a protein can be abnormally altered in response to external and internal cues, thus modulating cell physiology and contributing to human disease. In particular, neurodegenerative diseases due to the accumulation of aberrantly folded and aggregated proteins may lead to alterations in protein interactomes. Identifying changes in the interactomes of normal and disease states of proteins could help to understand molecular disease mechanisms, but current interactomics methods are limited in the ability to pinpoint structure-specific PPIs and their interaction interfaces on a proteome-wide scale. Here, we adapted limited proteolysis–mass spectrometry (LiP–MS) to systematically identify putative structure-specific PPIs by probing protein structural alterations within cellular extracts upon treatment with specific structural states of a given protein. We demonstrate the feasibility of our method to detect well-characterized PPIs, including antibody–target protein interactions and interactions with membrane proteins, and show that it pinpoints PPI interfaces. We then applied the LiP–MS approach to study the structure-specific interactors of the Parkinson’s disease hallmark protein alpha-synuclein (aSyn). We identified several previously known interactors of both aSyn monomer and amyloid fibrils and provide a resource of novel putative structure-specific interactors for further studies. This approach is applicable to identify structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound structural states of proteins.
Published: 2023

6. Structural strains of misfolded tau protein define different diseases

Author: Stahlberg, Henning, Riek, Roland, Stahlberg, Henning, and Riek, Roland
Abstract: In diseases called tauopathies, misfolded tau proteins form aggregates called fibrils. Fibrils from nine different tauopathies show that tau misfolds in many ways, enabling the diseases to be classified according to fibril structure.
Published: 2022
Full Text: View/download PDF

7. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

8. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

9. Atomic resolution protein allostery from the multi-state structure of a PDZ domain

Author: Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, Riek, Roland, Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, and Riek, Roland
Abstract: Recent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an "open" ligand welcoming state and a "closed" state that obstructs the binding site by changing the distance between the beta-sheet 2, alpha-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering similar to 25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.
Published: 2022
Full Text: View/download PDF

10. Atomic resolution protein allostery from the multi-state structure of a PDZ domain

Author: Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, Riek, Roland, Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, and Riek, Roland
Abstract: Recent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an "open" ligand welcoming state and a "closed" state that obstructs the binding site by changing the distance between the beta-sheet 2, alpha-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering similar to 25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.
Published: 2022
Full Text: View/download PDF

11. Atomic resolution protein allostery from the multi-state structure of a PDZ domain

Author: Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, Riek, Roland, Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, and Riek, Roland
Abstract: Recent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an "open" ligand welcoming state and a "closed" state that obstructs the binding site by changing the distance between the beta-sheet 2, alpha-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering similar to 25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.
Published: 2022
Full Text: View/download PDF

12. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

13. Atomic resolution protein allostery from the multi-state structure of a PDZ domain

Author: Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, Riek, Roland, Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, and Riek, Roland
Abstract: Recent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an "open" ligand welcoming state and a "closed" state that obstructs the binding site by changing the distance between the beta-sheet 2, alpha-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering similar to 25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.
Published: 2022
Full Text: View/download PDF

14. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

15. Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development

Author: State of Hesse, German Research Foundation, European Commission, Ministero dell'Istruzione, dell'Università e della Ricerca, Agence Nationale de la Recherche (France), Centre National de la Recherche Scientifique (France), National Institutes of Health (US), National Science Foundation (US), Latvian Council of Science, Berg, Hannes [0000-0002-2060-4296], Wirtz Martin, Maria A. [0000-0002-0318-7785], Altincekic, Nadide [0000-0001-6370-3414], Alshamleh, Islam [0000-0001-6714-3602], Dhamotharan, Karthikeyan [0000-0003-0226-7350], Marianne Korn, Sophie [0000-0003-3798-3277], Schulte, Linda [0000-0002-9334-8908], da Silva Almeida, Marcius [0000-0003-4921-8185], Caterina Felli, Isabella [0000-0002-6018-9090], Fourkiotis, Nikolaos K. [0000-0002-5197-4142], Gallo, Angelo [0000-0001-9778-4822], Ninot-Pedrosa, Martí [0000-0003-2851-9990], Pontoriero, Letizia [0000-0002-5586-1305], Treviño, Miguel A. [0000-0002-0738-5973], Tsika, Aikaterini C. [000-0002-3723-0606], Almeida, Fabio C.L. [0000-0001-6046-7006], Bax, Ad [0000-0002-9809-5700], Henzler-Wildman, Katherine [0000-0002-5295-2121], Hoch, Jeffrey C. [0000-0002-9230-2019], Jaudzems, Kristaps [0000-0003-3922-2447], Laurents, D.V. [0000-0002-4187-165X], Ferner, Jan [0000-0002-2009-3203], Hengesbach, Martin [0000-0001-9414-1602], Löhr, Frank [0000-0001-6399-9497], Qureshi, Nusrat [0000-0002-5753-5984], Richter, Christian [0000-0002-5420-2826], Schlundt, Andreas [0000-0003-2254-7560], Weigand, Julia E. [0000-0003-4247-1348], Wirmer-Bartoschek, Julia [0000-0002-0642-1311], Schwalbe, Harald [0000-0001-5693-7909], Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Marianne Korn, Sophie, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J.J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, da Silva Almeida, Marcius, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus-Antunes, Nathane, Mompeán, Miguel, Cristtina Neves-Martins, Thais, Ninot-Pedrosa, Martí, Pinheiro, Anderson S.., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel A., Tsika, Aikaterini C., Almeida, Fabio C.L., Bax, Ad, Henzler-Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt-Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer-Bartoschek, Julia, Wöhnert, Jens, Schwalbe, Harald, State of Hesse, German Research Foundation, European Commission, Ministero dell'Istruzione, dell'Università e della Ricerca, Agence Nationale de la Recherche (France), Centre National de la Recherche Scientifique (France), National Institutes of Health (US), National Science Foundation (US), Latvian Council of Science, Berg, Hannes [0000-0002-2060-4296], Wirtz Martin, Maria A. [0000-0002-0318-7785], Altincekic, Nadide [0000-0001-6370-3414], Alshamleh, Islam [0000-0001-6714-3602], Dhamotharan, Karthikeyan [0000-0003-0226-7350], Marianne Korn, Sophie [0000-0003-3798-3277], Schulte, Linda [0000-0002-9334-8908], da Silva Almeida, Marcius [0000-0003-4921-8185], Caterina Felli, Isabella [0000-0002-6018-9090], Fourkiotis, Nikolaos K. [0000-0002-5197-4142], Gallo, Angelo [0000-0001-9778-4822], Ninot-Pedrosa, Martí [0000-0003-2851-9990], Pontoriero, Letizia [0000-0002-5586-1305], Treviño, Miguel A. [0000-0002-0738-5973], Tsika, Aikaterini C. [000-0002-3723-0606], Almeida, Fabio C.L. [0000-0001-6046-7006], Bax, Ad [0000-0002-9809-5700], Henzler-Wildman, Katherine [0000-0002-5295-2121], Hoch, Jeffrey C. [0000-0002-9230-2019], Jaudzems, Kristaps [0000-0003-3922-2447], Laurents, D.V. [0000-0002-4187-165X], Ferner, Jan [0000-0002-2009-3203], Hengesbach, Martin [0000-0001-9414-1602], Löhr, Frank [0000-0001-6399-9497], Qureshi, Nusrat [0000-0002-5753-5984], Richter, Christian [0000-0002-5420-2826], Schlundt, Andreas [0000-0003-2254-7560], Weigand, Julia E. [0000-0003-4247-1348], Wirmer-Bartoschek, Julia [0000-0002-0642-1311], Schwalbe, Harald [0000-0001-5693-7909], Berg, Hannes, Wirtz Martin, Maria A., Altincekic, Nadide, Alshamleh, Islam, Kaur Bains, Jasleen, Blechar, Julius, Ceylan, Betül, Jesus, Vanessa de, Dhamotharan, Karthikeyan, Fuks, Christin, Gande, Santosh L., Hargittay, Bruno, Hohmann, Katharina F., Hutchison, Marie T., Marianne Korn, Sophie, Krishnathas, Robin, Kutz, Felicitas, Linhard, Verena, Matzel, Tobias, Meiser, Nathalie, Niesteruk, Anna, Pyper, Dennis J., Schulte, Linda, Trucks, Sven, Azzaoui, Kamal, Blommers, Marcel J.J., Gadiya, Yojana, Karki, Reagon, Zaliani, Andrea, Gribbon, Philip, da Silva Almeida, Marcius, Dinis Anobom, Cristiane, Bula, Anna L., Bütikofer, Matthias, Putinhon Caruso, Ícaro, Caterina Felli, Isabella, Da Poian, Andrea T., Cardoso de Amorim, Gisele, Fourkiotis, Nikolaos K., Gallo, Angelo, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Hao, Bing, Kurauskas, Vilius, Lecoq, Lauriane, Li, Yunfeng, Cunha Mebus-Antunes, Nathane, Mompeán, Miguel, Cristtina Neves-Martins, Thais, Ninot-Pedrosa, Martí, Pinheiro, Anderson S.., Pontoriero, Letizia, Pustovalova, Yulia, Riek, Roland, Robertson, Angus J., Jose Abi Saad, Marie, Treviño, Miguel A., Tsika, Aikaterini C., Almeida, Fabio C.L., Bax, Ad, Henzler-Wildman, Katherine, Hoch, Jeffrey C., Jaudzems, Kristaps, Laurents, Douglas V., Orts, Julien, Pierattelli, Roberta, Spyroulias, Georgios A., Duchardt-Ferner, Elke, Ferner, Jan, Fürtig, Boris, Hengesbach, Martin, Löhr, Frank, Qureshi, Nusrat, Richter, Christian, Saxena, Krishna, Schlundt, Andreas, Sreeramulu, Sridhar, Wacker, Anna, Weigand, Julia E., Wirmer-Bartoschek, Julia, Wöhnert, Jens, and Schwalbe, Harald
Abstract: SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.
Published: 2022

16. Structural strains of misfolded tau protein define different diseases

Author: Stahlberg, Henning, Riek, Roland, Stahlberg, Henning, and Riek, Roland
Abstract: In diseases called tauopathies, misfolded tau proteins form aggregates called fibrils. Fibrils from nine different tauopathies show that tau misfolds in many ways, enabling the diseases to be classified according to fibril structure.
Published: 2022
Full Text: View/download PDF

17. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

18. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

19. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, da Silva Almeida, Marcius, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2022

20. Rapid protein assignments and structures from raw NMR spectra with the deep learning technique ARTINA

Author: Klukowski, Piotr, Riek, Roland, Güntert, Peter, Klukowski, Piotr, Riek, Roland, and Güntert, Peter
Abstract: Nuclear Magnetic Resonance (NMR) spectroscopy is one of the major techniques in structural biology with over 11,800 protein structures deposited in the Protein Data Bank. NMR can elucidate structures and dynamics of small and medium size proteins in solution, living cells, and solids, but has been limited by the tedious data analysis process. It typically requires weeks or months of manual work of a trained expert to turn NMR measurements into a protein structure. Automation of this process is an open problem, formulated in the field over 30 years ago. Here, we present a solution to this challenge that enables the completely automated analysis of protein NMR data within hours after completing the measurements. Using only NMR spectra and the protein sequence as input, our machine learning-based method, ARTINA, delivers signal positions, resonance assignments, and structures strictly without any human intervention. Tested on a 100-protein benchmark comprising 1329 multidimensional NMR spectra, ARTINA demonstrated its ability to solve structures with 1.44 {\AA} median RMSD to the PDB reference and to identify 91.36% correct NMR resonance assignments. ARTINA can be used by non-experts, reducing the effort for a protein assignment or structure determination by NMR essentially to the preparation of the sample and the spectra measurements.
Published: 2022
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21. Atomic resolution protein allostery from the multi-state structure of a PDZ domain

Author: Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, Riek, Roland, Ashkinadze, Dzmitry, Kadavath, Harindranath, Pokharna, Aditya, Chi, Celestine, Friedmann, Michael, Strotz, Dean, Kumari, Pratibha, Minges, Martina, Cadalbert, Riccardo, Koenigl, Stefan, Guentert, Peter, Vogeli, Beat, and Riek, Roland
Abstract: Recent methodological advances in solution NMR allow the determination of multi-state protein structures and provide insights into structurally and dynamically correlated protein sites at atomic resolution. This is demonstrated in the present work for the well-studied PDZ2 domain of protein human tyrosine phosphatase 1E for which protein allostery had been predicted. Two-state protein structures were calculated for both the free form and in complex with the RA-GEF2 peptide using the exact nuclear Overhauser effect (eNOE) method. In the apo protein, an allosteric conformational selection step comprising almost 60% of the domain was detected with an "open" ligand welcoming state and a "closed" state that obstructs the binding site by changing the distance between the beta-sheet 2, alpha-helix 2, and sidechains of residues Lys38 and Lys72. The observed induced fit-type apo-holo structural rearrangements are in line with the previously published evolution-based analysis covering similar to 25% of the domain with only a partial overlap with the protein allostery of the open form. These presented structural studies highlight the presence of a dedicated highly optimized and complex dynamic interplay of the PDZ2 domain owed by the structure-dynamics landscape.
Published: 2022
Full Text: View/download PDF

22. Mass Photometry of Membrane Proteins

Author: Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Olerinyova, Anna, Sonn-Segev, Adar, Gault, Joseph, Eichmann, Cédric, Schimpf, Johannes, Kopf, Adrian H., Rudden, Lucas S.P., Ashkinadze, Dzmitry, Bomba, Radoslaw, Frey, Lukas, Greenwald, Jason, Degiacomi, Matteo T., Steinhilper, Ralf, Killian, J. Antoinette, Friedrich, Thorsten, Riek, Roland, Struwe, Weston B., Kukura, Philipp, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Olerinyova, Anna, Sonn-Segev, Adar, Gault, Joseph, Eichmann, Cédric, Schimpf, Johannes, Kopf, Adrian H., Rudden, Lucas S.P., Ashkinadze, Dzmitry, Bomba, Radoslaw, Frey, Lukas, Greenwald, Jason, Degiacomi, Matteo T., Steinhilper, Ralf, Killian, J. Antoinette, Friedrich, Thorsten, Riek, Roland, Struwe, Weston B., and Kukura, Philipp
Published: 2021

23. Mass Photometry of Membrane Proteins

Author: Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Olerinyova, Anna, Sonn-Segev, Adar, Gault, Joseph, Eichmann, Cédric, Schimpf, Johannes, Kopf, Adrian H., Rudden, Lucas S.P., Ashkinadze, Dzmitry, Bomba, Radoslaw, Frey, Lukas, Greenwald, Jason, Degiacomi, Matteo T., Steinhilper, Ralf, Killian, J. Antoinette, Friedrich, Thorsten, Riek, Roland, Struwe, Weston B., Kukura, Philipp, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Olerinyova, Anna, Sonn-Segev, Adar, Gault, Joseph, Eichmann, Cédric, Schimpf, Johannes, Kopf, Adrian H., Rudden, Lucas S.P., Ashkinadze, Dzmitry, Bomba, Radoslaw, Frey, Lukas, Greenwald, Jason, Degiacomi, Matteo T., Steinhilper, Ralf, Killian, J. Antoinette, Friedrich, Thorsten, Riek, Roland, Struwe, Weston B., and Kukura, Philipp
Published: 2021

24. The expanding amyloid family: Structure, stability, function, and pathogenesis.

Author: Sawaya, Michael R, Sawaya, Michael R, Hughes, Michael P, Rodriguez, Jose A, Riek, Roland, Eisenberg, David S, Sawaya, Michael R, Sawaya, Michael R, Hughes, Michael P, Rodriguez, Jose A, Riek, Roland, and Eisenberg, David S
Abstract: The hidden world of amyloid biology has suddenly snapped into atomic-level focus, revealing over 80 amyloid protein fibrils, both pathogenic and functional. Unlike globular proteins, amyloid proteins flatten and stack into unbranched fibrils. Stranger still, a single protein sequence can adopt wildly different two-dimensional conformations, yielding distinct fibril polymorphs. Thus, an amyloid protein may define distinct diseases depending on its conformation. At the heart of this conformational variability lies structural frustrations. In functional amyloids, evolution tunes frustration levels to achieve either stability or sensitivity according to the fibril's biological function, accounting for the vast versatility of the amyloid fibril scaffold.
Published: 2021

25. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., de Jesus, Vanessa, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, zur Lage, Susanne, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, Almeida, Marcius da Silva, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, de Amorim, Gisele Cardoso, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., de Jesus, Vanessa, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, zur Lage, Susanne, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, Almeida, Marcius da Silva, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel Á., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2021

26. Mass Photometry of Membrane Proteins

Author: Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Olerinyova, Anna, Sonn-Segev, Adar, Gault, Joseph, Eichmann, Cédric, Schimpf, Johannes, Kopf, Adrian H., Rudden, Lucas S.P., Ashkinadze, Dzmitry, Bomba, Radoslaw, Frey, Lukas, Greenwald, Jason, Degiacomi, Matteo T., Steinhilper, Ralf, Killian, J. Antoinette, Friedrich, Thorsten, Riek, Roland, Struwe, Weston B., Kukura, Philipp, Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Olerinyova, Anna, Sonn-Segev, Adar, Gault, Joseph, Eichmann, Cédric, Schimpf, Johannes, Kopf, Adrian H., Rudden, Lucas S.P., Ashkinadze, Dzmitry, Bomba, Radoslaw, Frey, Lukas, Greenwald, Jason, Degiacomi, Matteo T., Steinhilper, Ralf, Killian, J. Antoinette, Friedrich, Thorsten, Riek, Roland, Struwe, Weston B., and Kukura, Philipp
Published: 2021

27. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Altınçekiç, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, Amorim, Gisele Cardoso de, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., De Jesus, Vanessa, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, Katherine, Hoch, Jeffrey C., Hohmann, Katharina Felicitas, Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalnins, Gints, Kanepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Zur Lage, Susanne, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Perez, Laura Mariño, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Poian, Andrea T. da, Pyper, Dennis Joshua, Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, Almeida, Marcius da Silva, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tars, Kaspars, Torres, Felix, Töws, Sabrina, Trevino, Miguel A., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Altınçekiç, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, Amorim, Gisele Cardoso de, Anderson, Thomas K., Anobom, Cristiane D., Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Adriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., De Jesus, Vanessa, Dhamotharan, Karthikeyan, Felli, Isabella C., Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Ghosh, Dhiman, Gomes-Neto, Francisco, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, Katherine, Hoch, Jeffrey C., Hohmann, Katharina Felicitas, Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalnins, Gints, Kanepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Krishnathas, Robin, Kutz, Felicitas, Zur Lage, Susanne, Lambertz, Roderick, Lang, Andras, Laurents, Douglas, Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Malki, Anas, Bessa, Luiza Mamigonian, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Monaca, Elisa, Montserret, Roland, Perez, Laura Mariño, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Poian, Andrea T. da, Pyper, Dennis Joshua, Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Pinheiro, Anderson S., Sabbatella, Raffaele, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, Almeida, Marcius da Silva, Sprague-Piercy, Marc A., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tars, Kaspars, Torres, Felix, Töws, Sabrina, Trevino, Miguel A., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2021

28. Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Author: Goethe University Frankfurt am Main, German Research Foundation, Cassa di Risparmio di Firenze, European Commission, University of New Hampshire, The Free State of Thuringia, National Institutes of Health (US), National Science Foundation (US), Howard Hughes Medical Institute, Latvian Council of Science, Ministry of Development and Investments (Greece), Helmholtz Association, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Swiss National Science Foundation, Fonds National Suisse de la Recherche Scientifique, ETH Zurich, European Research Council, Université Grenoble Alpes, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, Instituto de Salud Carlos III, Boehringer Ingelheim Fonds, Ministero dell'Istruzione, dell'Università e della Ricerca, Polytechnic Foundation of Frankfurt am Main, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, Cardoso de Amorim, Gisele, Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Andriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Ghosh, Dhiman, Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Gomes-Neto, Francisco, Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Malki, Anas, Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Bessa, Luiza Mamigonian, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas V., Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Pinheiro, Anderson S.., Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Sabbatella, Raffaele, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, Silva Almeida, Marcius da, Sprague-Piercy, Marc A., Anderson, Thomas K., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel A., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Anobom, Cristiane D., Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, Schlundt, Andreas, Goethe University Frankfurt am Main, German Research Foundation, Cassa di Risparmio di Firenze, European Commission, University of New Hampshire, The Free State of Thuringia, National Institutes of Health (US), National Science Foundation (US), Howard Hughes Medical Institute, Latvian Council of Science, Ministry of Development and Investments (Greece), Helmholtz Association, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Swiss National Science Foundation, Fonds National Suisse de la Recherche Scientifique, ETH Zurich, European Research Council, Université Grenoble Alpes, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, Instituto de Salud Carlos III, Boehringer Ingelheim Fonds, Ministero dell'Istruzione, dell'Università e della Ricerca, Polytechnic Foundation of Frankfurt am Main, Altincekic, Nadide, Korn, Sophie Marianne, Qureshi, Nusrat Shahin, Dujardin, Marie, Ninot-Pedrosa, Martí, Abele, Rupert, Abi Saad, Marie Jose, Alfano, Caterina, Almeida, Fabio C. L., Alshamleh, Islam, Cardoso de Amorim, Gisele, Anorma, Chelsea, Bains, Jasleen Kaur, Bax, Andriaan, Blackledge, Martin, Blechar, Julius, Böckmann, Anja, Brigandat, Louis, Bula, Anna, Bütikofer, Matthias, Camacho-Zarco, Aldo R., Ghosh, Dhiman, Carlomagno, Teresa, Caruso, Icaro Putinhon, Ceylan, Betül, Chaikuad, Apirat, Chu, Feixia, Cole, Laura, Crosby, Marquise G., Jesus, Vanessa de, Dhamotharan, Karthikeyan, Felli, Isabella C., Gomes-Neto, Francisco, Ferner, Jan, Fleischmann, Yanick, Fogeron, Marie-Laure, Fourkiotis, Nikolaos K., Fuks, Christin, Fürtig, Boris, Gallo, Angelo, Gande, Santosh L., Gerez, Juan Atilio, Gorbatyuk, Oksana, Guseva, Serafima, Hacker, Carolin, Häfner, Sabine, Hao, Bing, Hargittay, Bruno, Henzler-Wildman, K., Hoch, Jeffrey C., Malki, Anas, Hohmann, Katharina F., Hutchison, Marie T., Jaudzems, Kristaps, Jović, Katarina, Kaderli, Janina, Kalniņš, Gints, Kaņepe, Iveta, Kirchdoerfer, Robert N., Kirkpatrick, John, Knapp, Stefan, Bessa, Luiza Mamigonian, Krishnathas, Robin, Kutz, Felicitas, Lage, Susanne zur, Lambertz, Roderick, Lang, Andras, Laurents, Douglas V., Lecoq, Lauriane, Linhard, Verena, Löhr, Frank, Martin, Rachel W., Matzel, Tobias, Maurin, Damien, McNutt, Seth W., Mebus-Antunes, Nathane Cunha, Meier, Beat H., Meiser, Nathalie, Mompeán, Miguel, Pinheiro, Anderson S.., Monaca, Elisa, Montserret, Roland, Mariño Perez, Laura, Moser, Celine, Muhle-Goll, Claudia, Neves-Martins, Thais Cristtina, Ni, Xiamonin, Norton-Baker, Brenna, Pierattelli, Roberta, Pontoriero, Letizia, Sabbatella, Raffaele, Pustovalova, Yulia, Ohlenschläger, Oliver, Orts, Julien, Da Poian, Andrea T., Pyper, Dennis J., Richter, Christian, Riek, Roland, Rienstra, Chad M., Robertson, Angus, Salvi, Nicola, Saxena, Krishna, Schulte, Linda, Schiavina, Marco, Schwalbe, Harald, Silber, Mara, Silva Almeida, Marcius da, Sprague-Piercy, Marc A., Anderson, Thomas K., Spyroulias, Georgios A., Sreeramulu, Sridhar, Tants, Jan-Niklas, Tārs, Kaspars, Torres, Felix, Töws, Sabrina, Treviño, Miguel A., Trucks, Sven, Tsika, Aikaterini C., Varga, Krisztina, Anobom, Cristiane D., Wang, Ying, Weber, Marco E., Weigand, Julia E., Wiedemann, Christoph, Wirmer-Bartoschek, Julia, Wirtz Martin, Maria Alexandra, Zehnder, Johannes, Hengesbach, Martin, and Schlundt, Andreas
Abstract: The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Published: 2021

29. Extending the eNOE data set of large proteins by evaluation of NOEs with unresolved diagonals

Author: Chi, Celestine, Strotz, Dean, Riek, Roland, Vögeli, Beat, Chi, Celestine, Strotz, Dean, Riek, Roland, and Vögeli, Beat
Abstract: The representation of a protein's spatial sampling at atomic resolution is fundamental for understanding its function. NMR has been established as the best-suited technique toward this goal for small proteins. However, the accessible information content rapidly deteriorates with increasing protein size. We have recently demonstrated that for small proteins distance restraints with an accuracy smaller than 0.1Å can be obtained by replacing traditional semi-quantitative Nuclear Overhauser Effects (NOEs) with exact NOEs (eNOE). The high quality of the data allowed us to calculate structural ensembles of the small model protein GB3 consisting of multiple rather than a single state. The analysis has been limited to small proteins because NOEs of spins with unresolved diagonal peaks cannot be used. Here we propose a simple approach to translate such NOEs into correct upper distance restraints, which opens access to larger biomolecules. We demonstrate that for 16kDa cyclophilin A the collection of such restraints extends the original 1254 eNOEs to 3471.
Published: 2021

30. Half a century of amyloids: past, present and future

Author: Ke, Pu Chun, Zhou, Ruhong, Serpell, Louise C., Riek, Roland, Knowles, Tuomas P. J., Lashuel, Hilal A., Gazit, Ehud, Hamley, Ian W., Davis, Thomas P., Fändrich, Marcus, Otzen, Daniel Erik, Chapman, Matthew R., Dobson, Christopher M., Eisenberg, David S., Mezzenga, Raffaele, Ke, Pu Chun, Zhou, Ruhong, Serpell, Louise C., Riek, Roland, Knowles, Tuomas P. J., Lashuel, Hilal A., Gazit, Ehud, Hamley, Ian W., Davis, Thomas P., Fändrich, Marcus, Otzen, Daniel Erik, Chapman, Matthew R., Dobson, Christopher M., Eisenberg, David S., and Mezzenga, Raffaele
Abstract: Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued development of new therapeutics. In basic science and engineering, the cross-β architecture has been a constant thread underlying the structural characteristics of pathological and functional amyloids, and realizing that amyloid structures can be both pathological and functional in nature has fuelled innovations in artificial amyloids, whose use today ranges from water purification to 3D printing. At the conclusion of a half century since Eanes and Glenner's seminal study of amyloids in humans, this review commemorates the occasion by documenting the major milestones in amyloid research to date, from the perspectives of structural biology, biophysics, medicine, microbiology, engineering and nanotechnology. We also discuss new challenges and opportunities to drive this interdisciplinary field moving forward.
Published: 2020
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31. Regulation of α-synuclein by chaperones in mammalian cells

Author: Burmann, Björn M., Gerez, Juan A., Matečko-burmann, Irena, Campioni, Silvia, Kumari, Pratibha, Ghosh, Dhiman, Mazur, Adam, Aspholm, Emelie E., Šulskis, Darius, Wawrzyniuk, Magdalena, Bock, Thomas, Schmidt, Alexander, Rüdiger, Stefan G. D., Riek, Roland, Hiller, Sebastian, Burmann, Björn M., Gerez, Juan A., Matečko-burmann, Irena, Campioni, Silvia, Kumari, Pratibha, Ghosh, Dhiman, Mazur, Adam, Aspholm, Emelie E., Šulskis, Darius, Wawrzyniuk, Magdalena, Bock, Thomas, Schmidt, Alexander, Rüdiger, Stefan G. D., Riek, Roland, and Hiller, Sebastian
Published: 2020

32. Protein Allostery at Atomic Resolution

Author: Strotz, Dean, Orts, Julien, Kadavath, Harindranath, Friedmann, Michael, Ghosh, Dhiman, Olsson, Simon, Chi, Celestine N., Pokharna, Aditya, Guentert, Peter, Vogeli, Beat, Riek, Roland, Strotz, Dean, Orts, Julien, Kadavath, Harindranath, Friedmann, Michael, Ghosh, Dhiman, Olsson, Simon, Chi, Celestine N., Pokharna, Aditya, Guentert, Peter, Vogeli, Beat, and Riek, Roland
Abstract: Protein allostery is a phenomenon involving the long range coupling between two distal sites in a protein. In order to elucidate allostery at atomic resoluion on the ligand-binding WW domain of the enzyme Pin1, multistate structures were calculated from exact nuclear Overhauser effect (eNOE). In its free form, the protein undergoes a microsecond exchange between two states, one of which is predisposed to interact with its parent catalytic domain. In presence of the positive allosteric ligand, the equilibrium between the two states is shifted towards domain-domain interaction, suggesting a population shift model. In contrast, the allostery-suppressing ligand decouples the side-chain arrangement at the inter-domain interface thereby reducing the inter-domain interaction. As such, this mechanism is an example of dynamic allostery. The presented distinct modes of action highlight the power of the interplay between dynamics and function in the biological activity of proteins.
Published: 2020
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33. Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy

Author: Ni, Ruiqing, Chen, Zhenyue, Gerez, Juan A., Shi, Gloria, Zhou, Quanyu, Riek, Roland, Nilsson, Peter, Razansky, Daniel, Klohs, Jan, Ni, Ruiqing, Chen, Zhenyue, Gerez, Juan A., Shi, Gloria, Zhou, Quanyu, Riek, Roland, Nilsson, Peter, Razansky, Daniel, and Klohs, Jan
Abstract: Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement, Funding Agencies|Vontobel-Stiftung; VetenskapsradetSwedish Research Council [2016-00748]; European Research CouncilEuropean Research Council (ERC) [ERC-2015CoG-682379]; H2020 Marie Sklodowska-Curie Actions [746430-MSIOAM]; Stiftung Synapsis -Alzheimer Forschung Schweiz AFS [2017 CDA-03]; ERA-NET NEURON [32NE30_173678/1]; SchweizerischerNationalfonds zur Forderung derWissenschaftlichen ForschungAustrian Science Fund (FWF) [320030_179277]
Published: 2020
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34. Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy

Author: Ni, Ruiqing; https://orcid.org/0000-0002-0793-2113, Chen, Zhenyue; https://orcid.org/0000-0001-9508-7521, Gerez, Juan A, Shi, Gloria, Zhou, Quanyu, Riek, Roland, Nilsson, K Peter R, Razansky, Daniel, Klohs, Jan, Ni, Ruiqing; https://orcid.org/0000-0002-0793-2113, Chen, Zhenyue; https://orcid.org/0000-0001-9508-7521, Gerez, Juan A, Shi, Gloria, Zhou, Quanyu, Riek, Roland, Nilsson, K Peter R, Razansky, Daniel, and Klohs, Jan
Abstract: Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.
Published: 2020

35. Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Author: Guerrero-Ferreira, Ricardo, Taylor, Nicholas M.I., Arteni, Ana-Andrea, Kumari, Pratibha, Mona, Daniel, Ringler, Philippe, Britschgi, Markus, Lauer, Matthias E, Makky, Ali, Verasdonck, Joeri, Riek, Roland, Melki, Ronald, Meier, Beat H, Böckmann, Anja, Bousset, Luc, Stahlberg, Henning, Guerrero-Ferreira, Ricardo, Taylor, Nicholas M.I., Arteni, Ana-Andrea, Kumari, Pratibha, Mona, Daniel, Ringler, Philippe, Britschgi, Markus, Lauer, Matthias E, Makky, Ali, Verasdonck, Joeri, Riek, Roland, Melki, Ronald, Meier, Beat H, Böckmann, Anja, Bousset, Luc, and Stahlberg, Henning
Published: 2019

36. Proteomics-Based Monitoring of Pathway Activity Reveals that Blocking Diacylglycerol Biosynthesis Rescues from Alpha-Synuclein Toxicity

Author: Soste, Martin, Charmpi, Konstantina, Lampert, Fabienne, Gerez, Juan Atilio, van Oostrum, Marc, Malinovska, Liliana, Boersema, Paul Jonathan, Prymaczok, Natalia Cecilia, Riek, Roland, Peter, Matthias, Vanni, Stefano, Beyer, Andreas, Picotti, Paola, Soste, Martin, Charmpi, Konstantina, Lampert, Fabienne, Gerez, Juan Atilio, van Oostrum, Marc, Malinovska, Liliana, Boersema, Paul Jonathan, Prymaczok, Natalia Cecilia, Riek, Roland, Peter, Matthias, Vanni, Stefano, Beyer, Andreas, and Picotti, Paola
Abstract: Proteinaceous inclusions containing alpha-synuclein (alpha-Syn) have been implicated in neuronal toxicity in Parkinson's disease, but the pathways that modulate toxicity remain enigmatic. Here, we used a targeted proteomic assay to simultaneously measure 269 pathway activation markers and proteins deregulated by alpha-Syn expression across a panel of 33 Saccharomyces cerevisiae strains that genetically modulate alpha-Syn toxicity. Applying multidimensional linear regression analysis to these data predicted Pah1, a phosphatase that catalyzes conversion of phosphatidic acid to diacylglycerol at the endoplasmic reticulum membrane, as an effector of rescue. Follow-up studies demonstrated that inhibition of Pahl activity ameliorates the toxic effects of alpha-Syn, indicate that the diacylglycerol branch of lipid metabolism could enhance alpha-Syn neuronal cytotoxicity, and suggest a link between alpha-Syn toxicity and the biology of lipid droplets.
Published: 2019

37. Proteomics-Based Monitoring of Pathway Activity Reveals that Blocking Diacylglycerol Biosynthesis Rescues from Alpha-Synuclein Toxicity

Author: Soste, Martin, Charmpi, Konstantina, Lampert, Fabienne, Gerez, Juan Atilio, van Oostrum, Marc, Malinovska, Liliana, Boersema, Paul Jonathan, Prymaczok, Natalia Cecilia, Riek, Roland, Peter, Matthias, Vanni, Stefano, Beyer, Andreas, Picotti, Paola, Soste, Martin, Charmpi, Konstantina, Lampert, Fabienne, Gerez, Juan Atilio, van Oostrum, Marc, Malinovska, Liliana, Boersema, Paul Jonathan, Prymaczok, Natalia Cecilia, Riek, Roland, Peter, Matthias, Vanni, Stefano, Beyer, Andreas, and Picotti, Paola
Abstract: Proteinaceous inclusions containing alpha-synuclein (alpha-Syn) have been implicated in neuronal toxicity in Parkinson's disease, but the pathways that modulate toxicity remain enigmatic. Here, we used a targeted proteomic assay to simultaneously measure 269 pathway activation markers and proteins deregulated by alpha-Syn expression across a panel of 33 Saccharomyces cerevisiae strains that genetically modulate alpha-Syn toxicity. Applying multidimensional linear regression analysis to these data predicted Pah1, a phosphatase that catalyzes conversion of phosphatidic acid to diacylglycerol at the endoplasmic reticulum membrane, as an effector of rescue. Follow-up studies demonstrated that inhibition of Pahl activity ameliorates the toxic effects of alpha-Syn, indicate that the diacylglycerol branch of lipid metabolism could enhance alpha-Syn neuronal cytotoxicity, and suggest a link between alpha-Syn toxicity and the biology of lipid droplets.
Published: 2019

38. Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Author: Guerrero-Ferreira, Ricardo, Taylor, Nicholas M.I., Arteni, Ana-Andrea, Kumari, Pratibha, Mona, Daniel, Ringler, Philippe, Britschgi, Markus, Lauer, Matthias E, Makky, Ali, Verasdonck, Joeri, Riek, Roland, Melki, Ronald, Meier, Beat H, Böckmann, Anja, Bousset, Luc, Stahlberg, Henning, Guerrero-Ferreira, Ricardo, Taylor, Nicholas M.I., Arteni, Ana-Andrea, Kumari, Pratibha, Mona, Daniel, Ringler, Philippe, Britschgi, Markus, Lauer, Matthias E, Makky, Ali, Verasdonck, Joeri, Riek, Roland, Melki, Ronald, Meier, Beat H, Böckmann, Anja, Bousset, Luc, and Stahlberg, Henning
Published: 2019

39. Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Author: Guerrero-Ferreira, Ricardo, Taylor, Nicholas M.I., Arteni, Ana-Andrea, Kumari, Pratibha, Mona, Daniel, Ringler, Philippe, Britschgi, Markus, Lauer, Matthias E, Makky, Ali, Verasdonck, Joeri, Riek, Roland, Melki, Ronald, Meier, Beat H, Böckmann, Anja, Bousset, Luc, Stahlberg, Henning, Guerrero-Ferreira, Ricardo, Taylor, Nicholas M.I., Arteni, Ana-Andrea, Kumari, Pratibha, Mona, Daniel, Ringler, Philippe, Britschgi, Markus, Lauer, Matthias E, Makky, Ali, Verasdonck, Joeri, Riek, Roland, Melki, Ronald, Meier, Beat H, Böckmann, Anja, Bousset, Luc, and Stahlberg, Henning
Published: 2019

40. Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins

Author: Jemth, Per, Karlsson, Elin, Vogeli, Beat, Guzovsky, Brenda, Andersson, Eva, Hultqvist, Greta, Dogan, Jakob, Guntert, Peter, Riek, Roland, Chi, Celestine N., Jemth, Per, Karlsson, Elin, Vogeli, Beat, Guzovsky, Brenda, Andersson, Eva, Hultqvist, Greta, Dogan, Jakob, Guntert, Peter, Riek, Roland, and Chi, Celestine N.
Abstract: In every established species, protein-protein interactions have evolved such that they are fit for purpose. However, the molecular details of the evolution of new protein-protein interactions are poorly understood. We have used nuclear magnetic resonance spectroscopy to investigate the changes in structure and dynamics during the evolution of a protein-protein interaction involving the intrinsically disordered CREBBP (CREB-binding protein) interaction domain (CID) and nuclear coactivator binding domain (NCBD) from the transcriptional coregulators NCOA (nuclear receptor coactivator) and CREBBP/p300, respectively. The most ancient low-affinity "Cambrian-like" [540 to 600 million years (Ma) ago] CID/NCBD complex contained less secondary structure and was more dynamic than the complexes from an evolutionarily younger "Ordovician-Silurian" fish ancestor (ca. 440 Ma ago) and extant human. The most ancient Cambrian-like CID/NCBD complex lacked one helix and several interdomain interactions, resulting in a larger solvent-accessible surface area. Furthermore, the most ancient complex had a high degree of millisecond-to-microsecond dynamics distributed along the entire sequences of both CID and NCBD. These motions were reduced in the Ordovician-Silurian CID/NCBD complex and further redistributed in the extant human CID/NCBD complex. Isothermal calorimetry experiments show that complex formation is enthalpically favorable and that affinity is modulated by a largely unfavorable entropic contribution to binding. Our data demonstrate how changes in structure and motion conspire to shape affinity during the evolution of a protein-protein complex and provide direct evidence for the role of structural, dynamic, and frustrational plasticity in the evolution of interactions between intrinsically disordered proteins.
Published: 2018
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41. Quantitative mass imaging of single biological macromolecules

Author: Young, Gavin, Hundt, Nikolas, Cole, Daniel, Fineberg, Adam, Andrecka, Joanna, Tyler, Andrew, Olerinyova, Anna, Ansari, Ayla, Marklund, Erik G., Collier, Miranda P., Chandler, Shane A., Tkachenko, Olga, Allen, Joel, Crispin, Max, Billington, Neil, Takagi, Yasuharu, Sellers, James R., Eichmann, Cédric, Selenko, Philipp, Frey, Lukas, Riek, Roland, Galpin, Martin R., Struwe, Weston B., Benesch, Justin L. P., Kukura, Philipp, Young, Gavin, Hundt, Nikolas, Cole, Daniel, Fineberg, Adam, Andrecka, Joanna, Tyler, Andrew, Olerinyova, Anna, Ansari, Ayla, Marklund, Erik G., Collier, Miranda P., Chandler, Shane A., Tkachenko, Olga, Allen, Joel, Crispin, Max, Billington, Neil, Takagi, Yasuharu, Sellers, James R., Eichmann, Cédric, Selenko, Philipp, Frey, Lukas, Riek, Roland, Galpin, Martin R., Struwe, Weston B., Benesch, Justin L. P., and Kukura, Philipp
Abstract: Careful measurements of light scattering can provide information on individual macromolecules and complexes. Young et al. used a light-scattering approach for accurate mass determination of proteins as small as 20 kDa (see the Perspective by Lee and Klenerman). Movies of protein complex association and dissociation were analyzed to extract biophysical parameters from single molecules and assemblies without labeling. Using this approach, the authors determined in vitro kinetics of fibril and aggregate growth and association constants for a complex protein-glycoprotein assembly.Science, this issue p. 423; see also p. 378The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.
Published: 2018
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42. NOE-derived methyl distances from a 360 kDa proteasome complex

Author: Chi, Celestine N., Strotz, Dean, Riek, Roland, Vögeli, Beat Rolf, Chi, Celestine N., Strotz, Dean, Riek, Roland, and Vögeli, Beat Rolf
Abstract: Nuclear magnetic resonance spectroscopy is the prime tool to probe structure and dynamics of biomolecules at atomic resolution. A serious challenge for that method is the size limit imposed on molecules to be studied. Standard studies are typically restricted to ca. 30-40 kDa. More recent developments lead to spin relaxation measurements in methyl groups in single proteins or protein complexes as large as a mega-Dalton, which directly allow the extraction of angular information or experiments with paramagnetic samples. However, these probes are all of indirect nature in contrast to the most intuitive and easy-to-interpret structural/dynamics restraint, the internuclear distance, which can be measured by nuclear Overhauser enhancement (NOE). Here, we demonstrate time-averaged distance measurements on the 360 kDa half proteasome from Thermoplasma acidophilium. The approach is based on exact quantification of the NOE (eNOE). Our findings open up an avenue for such measurements on very large molecules. These restraints will help in a detailed determination of conformational changes upon perturbation such as ligand binding.
Published: 2018
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43. Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins

Author: Jemth, Per, Karlsson, Elin, Vögeli, Beat, Guzovsky, Brenda, Andersson, Eva, Hultqvist, Greta, Dogan, Jakob, Güntert, Peter, Riek, Roland, Chi, Celestine N., Jemth, Per, Karlsson, Elin, Vögeli, Beat, Guzovsky, Brenda, Andersson, Eva, Hultqvist, Greta, Dogan, Jakob, Güntert, Peter, Riek, Roland, and Chi, Celestine N.
Abstract: In every established species, protein-protein interactions have evolved such that they are fit for purpose. However, the molecular details of the evolution of new protein-protein interactions are poorly understood. We have used nuclear magnetic resonance spectroscopy to investigate the changes in structure and dynamics during the evolution of a protein-protein interaction involving the intrinsically disordered CREBBP (CREB-binding protein) interaction domain (CID) and nuclear coactivator binding domain (NCBD) from the transcriptional coregulators NCOA (nuclear receptor coactivator) and CREBBP/p300, respectively. The most ancient low-affinity Cambrian-like [540 to 600 million years (Ma) ago] CID/NCBD complex contained less secondary structure and was more dynamic than the complexes from an evolutionarily younger Ordovician-Silurian fish ancestor (ca. 440 Ma ago) and extant human. The most ancient Cambrian-like CID/NCBD complex lacked one helix and several interdomain interactions, resulting in a larger solvent-accessible surface area. Furthermore, the most ancient complex had a high degree of millisecond-to-microsecond dynamics distributed along the entire sequences of both CID and NCBD. These motions were reduced in the Ordovician-Silurian CID/NCBD complex and further redistributed in the extant human CID/NCBD complex. Isothermal calorimetry experiments show that complex formation is enthalpically favorable and that affinity is modulated by a largely unfavorable entropic contribution to binding. Our data demonstrate how changes in structure and motion conspire to shape affinity during the evolution of a protein-protein complex and provide direct evidence for the role of structural, dynamic, and frustrational plasticity in the evolution of interactions between intrinsically disordered proteins.
Published: 2018
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44. Femtosecond X-ray coherent diffraction of aligned amyloid fibrils on low background graphene.

Author: Seuring, Carolin, Seuring, Carolin, Ayyer, Kartik, Filippaki, Eleftheria, Barthelmess, Miriam, Longchamp, Jean-Nicolas, Ringler, Philippe, Pardini, Tommaso, Wojtas, David H, Coleman, Matthew A, Dörner, Katerina, Fuglerud, Silje, Hammarin, Greger, Habenstein, Birgit, Langkilde, Annette E, Loquet, Antoine, Meents, Alke, Riek, Roland, Stahlberg, Henning, Boutet, Sébastien, Hunter, Mark S, Koglin, Jason, Liang, Mengning, Ginn, Helen M, Millane, Rick P, Frank, Matthias, Barty, Anton, Chapman, Henry N, Seuring, Carolin, Seuring, Carolin, Ayyer, Kartik, Filippaki, Eleftheria, Barthelmess, Miriam, Longchamp, Jean-Nicolas, Ringler, Philippe, Pardini, Tommaso, Wojtas, David H, Coleman, Matthew A, Dörner, Katerina, Fuglerud, Silje, Hammarin, Greger, Habenstein, Birgit, Langkilde, Annette E, Loquet, Antoine, Meents, Alke, Riek, Roland, Stahlberg, Henning, Boutet, Sébastien, Hunter, Mark S, Koglin, Jason, Liang, Mengning, Ginn, Helen M, Millane, Rick P, Frank, Matthias, Barty, Anton, and Chapman, Henry N
Abstract: Here we present a new approach to diffraction imaging of amyloid fibrils, combining a free-standing graphene support and single nanofocused X-ray pulses of femtosecond duration from an X-ray free-electron laser. Due to the very low background scattering from the graphene support and mutual alignment of filaments, diffraction from tobacco mosaic virus (TMV) filaments and amyloid protofibrils is obtained to 2.7 Å and 2.4 Å resolution in single diffraction patterns, respectively. Some TMV diffraction patterns exhibit asymmetry that indicates the presence of a limited number of axial rotations in the XFEL focus. Signal-to-noise levels from individual diffraction patterns are enhanced using computational alignment and merging, giving patterns that are superior to those obtainable from synchrotron radiation sources. We anticipate that our approach will be a starting point for further investigations into unsolved structures of filaments and other weakly scattering objects.
Published: 2018

45. Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins

Author: Jemth, Per, Karlsson, Elin, Vögeli, Beat, Guzovsky, Brenda, Andersson, Eva, Hultqvist, Greta, Dogan, Jakob, Güntert, Peter, Riek, Roland, Chi, Celestine N., Jemth, Per, Karlsson, Elin, Vögeli, Beat, Guzovsky, Brenda, Andersson, Eva, Hultqvist, Greta, Dogan, Jakob, Güntert, Peter, Riek, Roland, and Chi, Celestine N.
Abstract: In every established species, protein-protein interactions have evolved such that they are fit for purpose. However, the molecular details of the evolution of new protein-protein interactions are poorly understood. We have used nuclear magnetic resonance spectroscopy to investigate the changes in structure and dynamics during the evolution of a protein-protein interaction involving the intrinsically disordered CREBBP (CREB-binding protein) interaction domain (CID) and nuclear coactivator binding domain (NCBD) from the transcriptional coregulators NCOA (nuclear receptor coactivator) and CREBBP/p300, respectively. The most ancient low-affinity “Cambrian-like” [540 to 600 million years (Ma) ago] CID/NCBD complex contained less secondary structure and was more dynamic than the complexes from an evolutionarily younger “Ordovician-Silurian” fish ancestor (ca. 440 Ma ago) and extant human. The most ancient Cambrian-like CID/NCBD complex lacked one helix and several interdomain interactions, resulting in a larger solvent-accessible surface area. Furthermore, the most ancient complex had a high degree of millisecond-to-microsecond dynamics distributed along the entire sequences of both CID and NCBD. These motions were reduced in the Ordovician-Silurian CID/NCBD complex and further redistributed in the extant human CID/NCBD complex. Isothermal calorimetry experiments show that complex formation is enthalpically favorable and that affinity is modulated by a largely unfavorable entropic contribution to binding. Our data demonstrate how changes in structure and motion conspire to shape affinity during the evolution of a protein-protein complex and provide direct evidence for the role of structural, dynamic, and frustrational plasticity in the evolution of interactions between intrinsically disordered proteins.
Published: 2018

46. Femtosecond X-ray coherent diffraction of aligned amyloid fibrils on low background graphene

Author: Seuring, Carolin, Ayyer, Kartik, Filippaki, Eleftheria, Barthelmess, Miriam, Longchamp, Jean-Nicolas, Ringler, Philippe, Pardini, Tommaso, Wojtas, David H, Coleman, Matthew A, Dörner, Katerina, Fuglerud, Silje, Hammarin, Greger, Habenstein, Birgit, Langkilde, Annette E, Loquet, Antoine, Meents, Alke, Riek, Roland, Stahlberg, Henning, Boutet, Sébastien, Hunter, Mark S, Koglin, Jason, Liang, Mengning, Ginn, Helen M, Millane, Rick P, Frank, Matthias, Barty, Anton, Chapman, Henry N, Seuring, Carolin, Ayyer, Kartik, Filippaki, Eleftheria, Barthelmess, Miriam, Longchamp, Jean-Nicolas, Ringler, Philippe, Pardini, Tommaso, Wojtas, David H, Coleman, Matthew A, Dörner, Katerina, Fuglerud, Silje, Hammarin, Greger, Habenstein, Birgit, Langkilde, Annette E, Loquet, Antoine, Meents, Alke, Riek, Roland, Stahlberg, Henning, Boutet, Sébastien, Hunter, Mark S, Koglin, Jason, Liang, Mengning, Ginn, Helen M, Millane, Rick P, Frank, Matthias, Barty, Anton, and Chapman, Henry N
Abstract: Here we present a new approach to diffraction imaging of amyloid fibrils, combining a free-standing graphene support and single nanofocused X-ray pulses of femtosecond duration from an X-ray free-electron laser. Due to the very low background scattering from the graphene support and mutual alignment of filaments, diffraction from tobacco mosaic virus (TMV) filaments and amyloid protofibrils is obtained to 2.7 Å and 2.4 Å resolution in single diffraction patterns, respectively. Some TMV diffraction patterns exhibit asymmetry that indicates the presence of a limited number of axial rotations in the XFEL focus. Signal-to-noise levels from individual diffraction patterns are enhanced using computational alignment and merging, giving patterns that are superior to those obtainable from synchrotron radiation sources. We anticipate that our approach will be a starting point for further investigations into unsolved structures of filaments and other weakly scattering objects.
Published: 2018

47. Binding of Polythiophenes to Amyloids : Structural Mapping of the Pharmacophore

Author: Schuetz, Anne K., Hornemann, Simone, Waelti, Marielle A., Greuter, Ladina, Tiberi, Cinzia, Cadalbert, Riccardo, Gantner, Matthias, Riek, Roland, Hammarström, Per, Nilsson, Peter, Boeckmann, Anja, Aguzzi, Adriano, Meier, Beat H., Schuetz, Anne K., Hornemann, Simone, Waelti, Marielle A., Greuter, Ladina, Tiberi, Cinzia, Cadalbert, Riccardo, Gantner, Matthias, Riek, Roland, Hammarström, Per, Nilsson, Peter, Boeckmann, Anja, Aguzzi, Adriano, and Meier, Beat H.
Abstract: Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates. 560 We clarify the binding site and mode of two different polythiophenes to fibrils of the prion domain of the HET-s protein by solid-state NMR and correlate these findings with their fluorescence properties. We demonstrate how amyloid dyes recognize distinct binding sites with specific topological features. Regularly spaced surface charge patterns and well-accessible grooves on the fibril surface define the pharmacophore of the amyloid, which in turn determines the binding mode and fluorescence wavelength of the polythiophene., Funding Agencies|Swiss National Science Foundation [200020_159707, 200020_146757, 200020_147660]; French ANR [ANR-14-CE09-0024B]; European Research Council [ERC: 670958]
Published: 2018
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48. 13C, 15N Resonance Assignment of Parts of the HET-s Prion Protein in its Amyloid Form

Author: Siemer, Ansgar, Ritter, Christiane, Steinmetz, Michel, Ernst, Matthias, Riek, Roland, Meier, Beat, Siemer, Ansgar, Ritter, Christiane, Steinmetz, Michel, Ernst, Matthias, Riek, Roland, and Meier, Beat
Abstract: The partial 15N and 13C solid-state NMR resonance assignment of the HET-s prion protein fragment 218-289 in its amyloid form is presented. It is based on experiments measured at MAS frequencies in the range of 20-40kHz using exclusively adiabatic polarization-transfer schemes. The resonance assignment within each residue is based on two-dimensional 13C--13C correlation spectra utilizing the DREAM mixing scheme. The sequential linking of the assigned residues used a set of two- and three-dimensional 15N--13C correlation experiments. Almost all cross peaks visible in the spectra are assigned, but only resonances from 43 of the 78 amino-acid residues could be detected. The missing residues are thought to be highly disordered and/or highly dynamic giving rise to broad resonance lines that escaped detection in the experiments applied. The line widths of the observed resonances are narrow and comparable to line widths observed in micro-crystalline samples. The 43 assigned residues are located in two fragments of about 20 residues
Published: 2018

49. Stereospecific assignments in proteins using exact NOEs

Author: Orts, Julien, Vögeli, Beat, Riek, Roland, Güntert, Peter, Orts, Julien, Vögeli, Beat, Riek, Roland, and Güntert, Peter
Abstract: Recently developed methods to measure distances in proteins with high accuracy by "exact” nuclear Overhauser effects (eNOEs) make it possible to determine stereospecific assignments, which are particularly important to fully exploit the accuracy of the eNOE distance measurements. Stereospecific assignments are determined by comparing the eNOE-derived distances to protein structure bundles calculated without stereospecific assignments, or an independently determined crystal structure. The absolute and relative CYANA target function difference upon swapping the stereospecific assignment of a diastereotopic group yields the respective stereospecific assignment. We applied the method to the eNOE data set that has recently been obtained for the third immunoglobulin-binding domain of protein G (GB3). The 884 eNOEs provide relevant data for 47 of the total of 75 diastereotopic groups. Stereospecific assignments could be established for 45 diastereotopic groups (96%) using the X-ray structure, or for 27 diastereotopic groups (57%) using structures calculated with the eNOE data set without stereospecific assignments, all of which are in agreement with those determined previously. The latter case is relevant for structure determinations based on eNOEs. The accuracy of the eNOE distance measurements is crucial for making stereospecific assignments because applying the same method to the traditional NOE data set for GB3 with imprecise upper distance bounds yields only 13 correct stereospecific assignments using the X-ray structure or 2 correct stereospecific assignments using NMR structures calculated without stereospecific assignments
Published: 2018

50. Femtosecond X-ray coherent diffraction of aligned amyloid fibrils on low background graphene

Author: Seuring, Carolin, Ayyer, Kartik, Filippaki, Eleftheria, Barthelmess, Miriam, Longchamp, Jean-Nicolas, Ringler, Philippe, Pardini, Tommaso, Wojtas, David H, Coleman, Matthew A, Dörner, Katerina, Fuglerud, Silje, Hammarin, Greger, Habenstein, Birgit, Langkilde, Annette E, Loquet, Antoine, Meents, Alke, Riek, Roland, Stahlberg, Henning, Boutet, Sébastien, Hunter, Mark S, Koglin, Jason, Liang, Mengning, Ginn, Helen M, Millane, Rick P, Frank, Matthias, Barty, Anton, Chapman, Henry N, Seuring, Carolin, Ayyer, Kartik, Filippaki, Eleftheria, Barthelmess, Miriam, Longchamp, Jean-Nicolas, Ringler, Philippe, Pardini, Tommaso, Wojtas, David H, Coleman, Matthew A, Dörner, Katerina, Fuglerud, Silje, Hammarin, Greger, Habenstein, Birgit, Langkilde, Annette E, Loquet, Antoine, Meents, Alke, Riek, Roland, Stahlberg, Henning, Boutet, Sébastien, Hunter, Mark S, Koglin, Jason, Liang, Mengning, Ginn, Helen M, Millane, Rick P, Frank, Matthias, Barty, Anton, and Chapman, Henry N
Abstract: Here we present a new approach to diffraction imaging of amyloid fibrils, combining a free-standing graphene support and single nanofocused X-ray pulses of femtosecond duration from an X-ray free-electron laser. Due to the very low background scattering from the graphene support and mutual alignment of filaments, diffraction from tobacco mosaic virus (TMV) filaments and amyloid protofibrils is obtained to 2.7 Å and 2.4 Å resolution in single diffraction patterns, respectively. Some TMV diffraction patterns exhibit asymmetry that indicates the presence of a limited number of axial rotations in the XFEL focus. Signal-to-noise levels from individual diffraction patterns are enhanced using computational alignment and merging, giving patterns that are superior to those obtainable from synchrotron radiation sources. We anticipate that our approach will be a starting point for further investigations into unsolved structures of filaments and other weakly scattering objects.
Published: 2018

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