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542 results on '"Griffin, Patrick R."'

5. Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α

Author

A, Mu, Wales, Thomas E., Zhou, Haixia, Draga-Coletă, Sorin-Valeriu, Gorgulla, Christoph, Blackmore, Katherine A., Mittenbühler, Melanie J., Kim, Caroline R., Bogoslavski, Dina, Zhang, Qiuyang, Wang, Zi-Fu, Jedrychowski, Mark P., Seo, Hyuk-Soo, Song, Kijun, Xu, Andrew Z., Sebastian, Luke, Gygi, Steven P., Arthanari, Haribabu, Dhe-Paganon, Sirano, Griffin, Patrick R., Engen, John R., and Spiegelman, Bruce M.

Published
2023
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6. Federating Structural Models and Data: Outcomes from A Workshop on Archiving Integrative Structures

Author

Berman, Helen M, Adams, Paul D, Bonvin, Alexandre A, Burley, Stephen K, Carragher, Bridget, Chiu, Wah, DiMaio, Frank, Ferrin, Thomas E, Gabanyi, Margaret J, Goddard, Thomas D, Griffin, Patrick R, Haas, Juergen, Hanke, Christian A, Hoch, Jeffrey C, Hummer, Gerhard, Kurisu, Genji, Lawson, Catherine L, Leitner, Alexander, Markley, John L, Meiler, Jens, Montelione, Gaetano T, Phillips, George N, Prisner, Thomas, Rappsilber, Juri, Schriemer, David C, Schwede, Torsten, Seidel, Claus AM, Strutzenberg, Timothy S, Svergun, Dmitri I, Tajkhorshid, Emad, Trewhella, Jill, Vallat, Brinda, Velankar, Sameer, Vuister, Geerten W, Webb, Benjamin, Westbrook, John D, White, Kate L, and Sali, Andrej

Subjects
Biological Sciences, Computational Biology, Crystallography, X-Ray, Databases, Protein, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Conformation, Proteins, Biophysics
Abstract

Structures of biomolecular systems are increasingly computed by integrative modeling. In this approach, a structural model is constructed by combining information from multiple sources, including varied experimental methods and prior models. In 2019, a Workshop was held as a Biophysical Society Satellite Meeting to assess progress and discuss further requirements for archiving integrative structures. The primary goal of the Workshop was to build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are presented here.

Published
2019

7. Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling.

Author

Longbotham, James E, Chio, Cynthia M, Dharmarajan, Venkatasubramanian, Trnka, Michael J, Torres, Idelisse Ortiz, Goswami, Devrishi, Ruiz, Karen, Burlingame, Alma L, Griffin, Patrick R, and Fujimori, Danica Galonić

Subjects
Animals, Histones, Catalytic Domain, Protein Conformation, Models, Molecular, Retinoblastoma-Binding Protein 2, Sf9 Cells, Protein Domains, Cancer, Genetics, 2.1 Biological and endogenous factors, Models, Molecular, MD Multidisciplinary
Abstract

Histone demethylase KDM5A removes methyl marks from lysine 4 of histone H3 and is often overexpressed in cancer. The in vitro demethylase activity of KDM5A is allosterically enhanced by binding of its product, unmodified H3 peptides, to its PHD1 reader domain. However, the molecular basis of this allosteric enhancement is unclear. Here we show that saturation of the PHD1 domain by the H3 N-terminal tail peptides stabilizes binding of the substrate to the catalytic domain and improves the catalytic efficiency of demethylation. When present in saturating concentrations, differently modified H3 N-terminal tail peptides have a similar effect on demethylation. However, they vary greatly in their affinity towards the PHD1 domain, suggesting that H3 modifications can tune KDM5A activity. Furthermore, hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) experiments reveal conformational changes in the allosterically enhanced state. Our findings may enable future development of anti-cancer therapies targeting regions involved in allosteric regulation.

Published
2019

8. Dual-mechanism estrogen receptor inhibitors

Author

Min, Jian, Nwachukwu, Jerome C., Min, Charles K., Njeri, Jacqline W., Srinivasan, Sathish, Rangarajan, Erumbi S., Nettles, Charles C., Guillen, Valeria Sanabria, Ziegler, Yvonne, Yan, Shunchao, Carlson, Kathryn E., Hou, Yingwei, Kim, Sung Hoon, Novick, Scott, Pascal, Bruce D., Houtman, Rene, Griffin, Patrick R., Izard, Tina, Katzenellenbogen, Benita S., Katzenellenbogen, John A., and Nettles, Kendall W.

Published
2021

9. Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection

Author

Wei, Guochao, Iqbal, Naseer, Courouble, Valentine V., Francis, Ashwanth C., Singh, Parmit K., Hudait, Arpa, Annamalai, Arun S., Bester, Stephanie, Huang, Szu-Wei, Shkriabai, Nikoloz, Briganti, Lorenzo, Haney, Reed, KewalRamani, Vineet N., Voth, Gregory A., Engelman, Alan N., Melikyan, Gregory B., Griffin, Patrick R., Asturias, Francisco, and Kvaratskhelia, Mamuka

Published
2022
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11. Structural Basis for the RNA-Guided Ribonuclease Activity of CRISPR-Cas13d

Author

Zhang, Cheng, Konermann, Silvana, Brideau, Nicholas J, Lotfy, Peter, Wu, Xuebing, Novick, Scott J, Strutzenberg, Timothy, Griffin, Patrick R, Hsu, Patrick D, and Lyumkis, Dmitry

Subjects
Genetics, Bioengineering, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Quality Education, CRISPR-Cas Systems, Clustered Regularly Interspaced Short Palindromic Repeats, Cryoelectron Microscopy, Endonucleases, HEK293 Cells, Humans, Molecular Conformation, RNA, RNA, Guide, Kinetoplastida, Ribonucleases, CRISPR, Cas13, Cas13d, Cas9, RNA interference, RNA targeting, cryo-EM, shRNA, structure, type VI, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

CRISPR-Cas endonucleases directed against foreign nucleic acids mediate prokaryotic adaptive immunity and have been tailored for broad genetic engineering applications. Type VI-D CRISPR systems contain the smallest known family of single effector Cas enzymes, and their signature Cas13d ribonuclease employs guide RNAs to cleave matching target RNAs. To understand the molecular basis for Cas13d function and explain its compact molecular architecture, we resolved cryoelectron microscopy structures of Cas13d-guide RNA binary complex and Cas13d-guide-target RNA ternary complex to 3.4 and 3.3 Å resolution, respectively. Furthermore, a 6.5 Å reconstruction of apo Cas13d combined with hydrogen-deuterium exchange revealed conformational dynamics that have implications for RNA scanning. These structures, together with biochemical and cellular characterization, provide insights into its RNA-guided, RNA-targeting mechanism and delineate a blueprint for the rational design of improved transcriptome engineering technologies.

Published
2018

12. MT-125 Inhibits Non-Muscle Myosin IIA and IIB, Synergizes with Oncogenic Kinase Inhibitors, and Prolongs Survival in Glioblastoma

Author

Kenchappa, Rajappa, primary, Radnai, Laszlo, additional, Young, Erica J, additional, Zarco, Natanael, additional, Lin, Li, additional, Dovas, Athanassios, additional, Meyer, Christian T, additional, Haddock, Ashley, additional, Hall, Alice, additional, Canoll, Peter T, additional, Cameron, Michael, additional, Nagaiah, Naveen K, additional, Rumbaugh, Gavin, additional, Griffin, Patrick R, additional, Kamenecka, Theodore M, additional, Miller, Courtney A, additional, and Rosenfeld, Steven S, additional

Published
2024
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14. GABAB receptor allosteric modulators exhibit pathway‐dependent and species‐selective activity

Author

Sturchler, Emmanuel, Li, Xia, Ladino, Maria Lourdes, Kaczanowska, Kasia, Cameron, Michael, Griffin, Patrick R, Finn, MG, Markou, Athina, and McDonald, Patricia

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Substance Misuse, Neurosciences, Tobacco Smoke and Health, Tobacco, Brain Disorders, Drug Abuse (NIDA only), Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Allosteric modulator, biased signaling, functional selectivity, GABA(B) receptor, ortholog selectivity, GABAB receptor, Medicinal and Biomolecular Chemistry, Pharmacology and pharmaceutical sciences
Abstract

Positive modulation of the GABAB receptor (GABABR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABABR GS39783 and BHF177 enhance GABA-stimulated [35S]GTP γS-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties. Extensive in vitro characterization of GS39783, BHF177, and NVP998 activity on GABABR-regulated signaling events, including modulation of cAMP, intracellular calcium levels, and ERK activation, revealed that these structurally related molecules display distinct pathway-specific signaling activities that correlate with the dissimilarities observed in rodent models and may be predictive of in vivo efficacy. Furthermore, these GABABR allosteric modulators exhibit species-dependent activity. Collectively, these data will be useful in guiding the development of GABABR allosteric modulators that display optimal in vivo efficacy in a preclinical model of nicotine dependence, and will identify those that have the potential to lead to novel antismoking therapies.

Published
2017

16. Structural insights into IMP2 dimerization and RNA binding

Author

Zorc, Stephen, primary, Munoz-Tello, Paola, additional, O'Leary, Timothy, additional, Yu, Xiaoyu, additional, Nag, Mithun, additional, Hansel-Harris, Althea, additional, Forli, Stefano, additional, Griffin, Patrick R., additional, Kojetin, Douglas J., additional, Roy, Raktim N., additional, and Janiszewska, Michalina, additional

Published
2024
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17. The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria

Author

Long, Jonathan Z, Svensson, Katrin J, Bateman, Leslie A, Lin, Hua, Kamenecka, Theodore, Lokurkar, Isha A, Lou, Jesse, Rao, Rajesh R, Chang, Mi Ra, Jedrychowski, Mark P, Paulo, Joao A, Gygi, Steven P, Griffin, Patrick R, Nomura, Daniel K, and Spiegelman, Bruce M

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Nutrition, Biotechnology, Obesity, Diabetes, 1.1 Normal biological development and functioning, Underpinning research, Adipocytes, Amidohydrolases, Amino Acids, Animals, Cell Respiration, Energy Metabolism, Fatty Acids, Glucose, Homeostasis, Male, Metabolic Networks and Pathways, Mice, Mice, Inbred C57BL, Mitochondria, Mitochondrial Proteins, Thermogenesis, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders.

Published
2016

22. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

Author

Kang, Yanyong, Zhou, X Edward, Gao, Xiang, He, Yuanzheng, Liu, Wei, Ishchenko, Andrii, Barty, Anton, White, Thomas A, Yefanov, Oleksandr, Han, Gye Won, Xu, Qingping, de Waal, Parker W, Ke, Jiyuan, Tan, MH Eileen, Zhang, Chenghai, Moeller, Arne, West, Graham M, Pascal, Bruce D, Van Eps, Ned, Caro, Lydia N, Vishnivetskiy, Sergey A, Lee, Regina J, Suino-Powell, Kelly M, Gu, Xin, Pal, Kuntal, Ma, Jinming, Zhi, Xiaoyong, Boutet, Sébastien, Williams, Garth J, Messerschmidt, Marc, Gati, Cornelius, Zatsepin, Nadia A, Wang, Dingjie, James, Daniel, Basu, Shibom, Roy-Chowdhury, Shatabdi, Conrad, Chelsie E, Coe, Jesse, Liu, Haiguang, Lisova, Stella, Kupitz, Christopher, Grotjohann, Ingo, Fromme, Raimund, Jiang, Yi, Tan, Minjia, Yang, Huaiyu, Li, Jun, Wang, Meitian, Zheng, Zhong, Li, Dianfan, Howe, Nicole, Zhao, Yingming, Standfuss, Jörg, Diederichs, Kay, Dong, Yuhui, Potter, Clinton S, Carragher, Bridget, Caffrey, Martin, Jiang, Hualiang, Chapman, Henry N, Spence, John CH, Fromme, Petra, Weierstall, Uwe, Ernst, Oliver P, Katritch, Vsevolod, Gurevich, Vsevolod V, Griffin, Patrick R, Hubbell, Wayne L, Stevens, Raymond C, Cherezov, Vadim, Melcher, Karsten, and Xu, H Eric

Subjects
1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Arrestin, Binding Sites, Crystallography, X-Ray, Disulfides, Humans, Lasers, Mice, Models, Molecular, Multiprotein Complexes, Protein Binding, Reproducibility of Results, Rhodopsin, Signal Transduction, X-Rays, General Science & Technology
Abstract

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.

Published
2015

26. Ablation of PM20D1 reveals N -acyl amino acid control of metabolism and nociception

Author

Long, Jonathan Z., Roche, Alexander M., Berdan, Charles A., Louie, Sharon M., Roberts, Amanda J., Svensson, Katrin J., Dou, Florence Y., Bateman, Leslie A., Mina, Amir I., Deng, Zhaoming, Jedrychowski, Mark P., Lin, Hua, Kamenecka, Theodore M., Asara, John M., Griffin, Patrick R., Banks, Alexander S., Nomura, Daniel K., and Spiegelman, Bruce M.

Published
2018

29. Recommendations for performing, interpreting and reporting hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments

Author

Masson, Glenn R., Burke, John E., Ahn, Natalie G., Anand, Ganesh S., Borchers, Christoph, Brier, Sébastien, Bou-Assaf, George M., Engen, John R., Englander, S. Walter, Faber, Johan, Garlish, Rachel, Griffin, Patrick R., Gross, Michael L., Guttman, Miklos, Hamuro, Yoshitomo, Heck, Albert J. R., Houde, Damian, Iacob, Roxana E., Jørgensen, Thomas J. D., Kaltashov, Igor A., Klinman, Judith P., Konermann, Lars, Man, Petr, Mayne, Leland, Pascal, Bruce D., Reichmann, Dana, Skehel, Mark, Snijder, Joost, Strutzenberg, Timothy S., Underbakke, Eric S., Wagner, Cornelia, Wales, Thomas E., Walters, Benjamin T., Weis, David D., Wilson, Derek J., Wintrode, Patrick L., Zhang, Zhongqi, Zheng, Jie, Schriemer, David C., and Rand, Kasper D.

Published
2019
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31. Structure of the photoreceptor synaptic assembly of the extracellular matrix protein pikachurin with the orphan receptor GPR179

Author

Patil, Dipak N., primary, Pantalone, Serena, additional, Cao, Yan, additional, Laboute, Thibaut, additional, Novick, Scott J., additional, Singh, Shikha, additional, Savino, Simone, additional, Faravelli, Silvia, additional, Magnani, Francesca, additional, Griffin, Patrick R., additional, Singh, Appu K., additional, Forneris, Federico, additional, and Martemyanov, Kirill A., additional

Published
2023
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35. The AP-1-BATF and -BATF3 module is essential for growth, survival and TH17/ILC3 skewing of anaplastic large cell lymphoma

Author

Schleussner, Nikolai, Merkel, Olaf, Costanza, Mariantonia, Liang, Huan-Chang, Hummel, Franziska, Romagnani, Chiara, Durek, Pawel, Anagnostopoulos, Ioannis, Hummel, Michael, Jöhrens, Korinna, Niedobitek, Antonia, Griffin, Patrick R., Piva, Roberto, Sczakiel, Henrike L., Woessmann, Wilhelm, Damm-Welk, Christine, Hinze, Christian, Stoiber, Dagmar, Gillissen, Bernd, Turner, Suzanne D., Kaergel, Eva, von Hoff, Linda, Grau, Michael, Lenz, Georg, Dörken, Bernd, Scheidereit, Claus, Kenner, Lukas, Janz, Martin, and Mathas, Stephan

Published
2018
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36. PPARγ Corepression Involves Alternate Ligand Conformation and Inflation of H12 Ensembles

Author

Frkic, Rebecca L., primary, Pederick, Jordan L., additional, Horsfall, Aimee J., additional, Jovcevski, Blagojce, additional, Crame, Elise E., additional, Kowalczyk, Wioleta, additional, Pukala, Tara L., additional, Chang, Mi Ra, additional, Zheng, Jie, additional, Blayo, Anne-Laure, additional, Abell, Andrew D., additional, Kamenecka, Theodore M., additional, Harbort, Joshua S., additional, Harmer, Jeffrey R., additional, Griffin, Patrick R, additional, and Bruning, John B., additional

Published
2023
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38. Biophysical Interactions of Direct AMPK Activators

Author

Kurumbail, Ravi G., primary, West, Graham M., additional, Dharmarajan, Venkatasubramanian, additional, Borzilleri, Kris A., additional, Withka, Jane M., additional, Ward, Jessica, additional, Reyes, Allan R., additional, Rajamohan, Francis, additional, Griffin, Patrick R., additional, and Calabrese, Matthew F., additional

Published
2018
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42. Structure of the full-length glucagon class B G-protein-coupled receptor

Author

Zhang, Haonan, Qiao, Anna, Yang, Dehua, Yang, Linlin, Dai, Antao, de Graaf, Chris, Reedtz-Runge, Steffen, Dharmarajan, Venkatasubramanian, Zhang, Hui, Han, Gye Won, Grant, Thomas D., Sierra, Raymond G., Weierstall, Uwe, Nelson, Garrett, Liu, Wei, Wu, Yanhong, Ma, Limin, Cai, Xiaoqing, Lin, Guangyao, Wu, Xiaoai, Geng, Zhi, Dong, Yuhui, Song, Gaojie, Griffin, Patrick R., Lau, Jesper, Cherezov, Vadim, Yang, Huaiyu, Hanson, Michael A., Stevens, Raymond C., Zhao, Qiang, Jiang, Hualiang, Wang, Ming-Wei, and Wu, Beili

Published
2017
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44. Patient-derived Siglec-6-targeting antibodies engineered for T-cell recruitment have potential therapeutic utility in chronic lymphocytic leukemia

Author

Cyr, Matthew G, primary, Mhibik, Maissa, additional, Qi, Junpeng, additional, Peng, Haiyong, additional, Chang, Jing, additional, Gaglione, Erika M, additional, Eik, David, additional, Herrick, John, additional, Venables, Thomas, additional, Novick, Scott J, additional, Courouble, Valentine V, additional, Griffin, Patrick R, additional, Wiestner, Adrian, additional, and Rader, Christoph, additional

Published
2022
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50. Structural basis of interdomain communication in PPARγ

Author

Mosure, Sarah A., primary, Munoz-Tello, Paola, additional, Kuo, Kuang-Ting, additional, MacTavish, Brian, additional, Yu, Xiaoyu, additional, Scholl, Daniel, additional, Williams, Christopher C., additional, Strutzenberg, Timothy S., additional, Bass, Jared, additional, Brust, Richard, additional, Deniz, Ashok A., additional, Griffin, Patrick R., additional, and Kojetin, Douglas J., additional

Published
2022
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