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36 results on '"Institute of Complex Systems (ICS)"'

1. Molecular mechanism of light-driven sodium pumping

Author: Kovalev, Kirill, Astashkin, Roman, Gushchin, Ivan, Orekhov, Philipp, Volkov, Dmytro, Zinovev, Egor, Marin, Egor, Rulev, Maksim, Alekseev, Alexey, Royant, Antoine, Carpentier, Philippe, Vaganova, Svetlana, Zabelskii, Dmitrii, Baeken, Christian, Sergeev, Ilya, Balandin, Taras, Bourenkov, Gleb, Carpena, Xavier, Boer, Roeland, Maliar, Nina, Borshchevskiy, Valentin, Büldt, Georg, Bamberg, Ernst, Gordeliy, Valentin, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow, Moscow Institute of Physics and Technology [Moscow] (MIPT), Biocatalyse (BIOCAT), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), European Synchrotron Radiation Facility (ESRF), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, European Molecular Biology Laboratory [Hamburg] (EMBL), Max-Planck-Institut für Biophysik - Max Planck Institute of Biophysics (MPIBP), Max-Planck-Gesellschaft, and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Subjects: Protein Folding, Rhodopsin, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Science, Sodium, Molecular Dynamics Simulation, Crystallography, X-Ray, Article, Bacterial Proteins, X-Ray Diffraction, Escherichia coli, lcsh:Q, ddc:500, Sodium-Potassium-Exchanging ATPase, lcsh:Science, Flavobacteriaceae, Ion transport, X-ray crystallography
Abstract: Nature Communications 11(1), 2137 (2020). doi:10.1038/s41467-020-16032-y, The light-driven sodium-pumping rhodopsin KR2 from Krokinobacter eikastus is the only non-proton cation active transporter with demonstrated potential for optogenetics. However, the existing structural data on KR2 correspond exclusively to its ground state, and show no sodium inside the protein, which hampers the understanding of sodium-pumping mechanism. Here we present crystal structure of the O-intermediate of the physiologically relevant pentameric form of KR2 at the resolution of 2.1 Å, revealing a sodium ion near the retinal Schiff base, coordinated by N112 and D116 of the characteristic NDQ triad. We also obtained crystal structures of D116N and H30A variants, conducted metadynamics simulations and measured pumping activities of putative pathway mutants to demonstrate that sodium release likely proceeds alongside Q78 towards the structural sodium ion bound between KR2 protomers. Our findings highlight the importance of pentameric assembly for sodium pump function, and may be used for rational engineering of enhanced optogenetic tools., Published by Nature Publishing Group UK, [London]
Published: 2020
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2. Symmetry-breaking transitions in the early steps of protein self-assembly

Author: Giuseppe Compagnini, Antonio Raudino, Martina Pannuzzo, Carmelo La Rosa, Danilo Milardi, Franca Fraternali, Fabio Lolicato, Birgit Strodel, Human Rezaei, Francesca Collu, Marcello Condorelli, Trang Nhu Do, Ayyalusamy Ramamoorthy, Mikko Karttunen, University of Catania [Italy], Department of Physics [Helsinki], Falculty of Science [Helsinki], University of Helsinki-University of Helsinki, Biochemistry Center Heidelberg (BZH), CNR – Istituto di Biostrutture e Bioimmagini, University of Waterloo [Waterloo], University of Western Ontario (UWO), Istituto Italiano di Tecnologia (IIT), University of Michigan [Ann Arbor], University of Michigan System, King‘s College London, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Natural Sciences and Engineering Council (NSERC) of Canada, Italian MIUR program PRIN 20157WZM8A, Progetto di Dipartimento 2017–2020, Swiss National Science Foundation, and EU Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant no. 754490
Subjects: 0301 basic medicine, Protein Denaturation, Protein Folding, 030103 biophysics, Amyloid, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Dimer, Biophysics, Peptide, Molecular dynamics, Molecular Dynamics Simulation, Spectrum Analysis, Raman, Intrinsically disordered proteins, Analytical model, Protein Structure, Secondary, Electrolytes, 03 medical and health sciences, chemistry.chemical_compound, ddc:570, Humans, Computer Simulation, Symmetry-breaking, Colloids, Symmetry breaking, chemistry.chemical_classification, Reproducibility of Results, General Medicine, Models, Theoretical, Islet Amyloid Polypeptide, Kinetics, 030104 developmental biology, chemistry, Oligomers, Solvents, Thermodynamics, Protein folding, Self-assembly, Protein Multimerization, Peptides
Abstract: International audience; Protein misfolding and subsequent self-association are complex, intertwined processes, resulting in development of a heterogeneous population of aggregates closely related to many chronic pathological conditions including Type 2 Diabetes Mellitus and Alzheimer’s disease. To address this issue, here, we develop a theoretical model in the general framework of linear stability analysis. According to this model, self-assemblies of peptides with pronounced conformational flexibility may become, under particular conditions, unstable and spontaneously evolve toward an alternating array of partially ordered and disordered monomers. The predictions of the theory were verified by atomistic molecular dynamics (MD) simulations of islet amyloid polypeptide (IAPP) used as a paradigm of aggregation-prone polypeptides (proteins). Simulations of dimeric, tetrameric, and hexameric human-IAPP self-assemblies at physiological electrolyte concentration reveal an alternating distribution of the smallest domains (of the order of the peptide mean length) formed by partially ordered (mainly β-strands) and disordered (turns and coil) arrays. Periodicity disappears upon weakening of the inter-peptide binding, a result in line with the predictions of the theory. To further probe the general validity of our hypothesis, we extended the simulations to other peptides, the Aβ(1–40) amyloid peptide, and the ovine prion peptide as well as to other proteins (SOD1 dimer) that do not belong to the broad class of intrinsically disordered proteins. In all cases, the oligomeric aggregates show an alternate distribution of partially ordered and disordered monomers. We also carried out Surface Enhanced Raman Scattering (SERS) measurements of hIAPP as an experimental validation of both the theory and in silico simulations.
Published: 2020
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3. True-atomic-resolution insights into the structure and functional role of linear chains and low-barrier hydrogen bonds in proteins

Author: Valentin Borshchevskiy, Kirill Kovalev, Ekaterina Round, Rouslan Efremov, Roman Astashkin, Gleb Bourenkov, Dmitry Bratanov, Taras Balandin, Igor Chizhov, Christian Baeken, Ivan Gushchin, Alexander Kuzmin, Alexey Alekseev, Andrey Rogachev, Dieter Willbold, Martin Engelhard, Ernst Bamberg, Georg Büldt, Valentin Gordeliy, Moscow Institute of Physics and Technology [Moscow] (MIPT), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, European X-ray Free Electron Laser GmbH, Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), DESY, European Mol Biol Lab, D-22607 Hamburg, Germany, Institute of Biological Information Processing [Jülich] (IBI-7), Institute for Biophysical Chemistry, Hannover Medical School [Hannover] (MHH), Jülich Center for Structural Biology [Jülich] (JuStruct), Research Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow, Institut für Physikalische Biologie [Düsseldorfd], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Max Planck Institute of Molecular Physiology, Max-Planck-Gesellschaft, and Department of Structural Biology, Max-Planck-Institute of Biophysics, Frankfurt, Germany
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Structural Biology, Proteins, MESH: Proteins, Hydrogen Bonding, MESH: Hydrogen Bonding, MESH: Protons, Protons, Molecular Biology
Abstract: International audience; Hydrogen bonds are fundamental to the structure and function of biological macromolecules and have been explored in detail. The chains of hydrogen bonds (CHBs) and low-barrier hydrogen bonds (LBHBs) were proposed to play essential roles in enzyme catalysis and proton transport. However, high-resolution structural data from CHBs and LBHBs is limited. The challenge is that their 'visualization' requires ultrahigh-resolution structures of the ground and functionally important intermediate states to identify proton translocation events and perform their structural assignment. Our true-atomic-resolution structures of the light-driven proton pump bacteriorhodopsin, a model in studies of proton transport, show that CHBs and LBHBs not only serve as proton pathways, but also are indispensable for long-range communications, signaling and proton storage in proteins. The complete picture of CHBs and LBHBs discloses their multifunctional roles in providing protein functions and presents a consistent picture of proton transport and storage resolving long-standing debates and controversies.
Published: 2021
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4. Molecular adaptations of NADP-malic enzyme for its function in C4 photosynthesis in grasses

Author: Martin J. Lercher, Luitgard Nagel-Steger, Alejandro Buschiazzo, Astrid Höppner, Anastasiia Bovdilova, Maria F. Drincovich, Mariana Saigo, Clarisa E. Alvarez, Veronica G. Maurino, Tao Zhang, Christian-Claus Wolff, Felipe Trajtenberg, Universidad Nacional de Rosario [Santa Fe], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Cluster of Excellence on Plant Sciences (CEPLAS), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]-Max Planck Institute for Plant Breeding Research (MPIPZ)-Universität zu Köln = University of Cologne, Molecular and structural microbiology / Microbiología Molecular y Estructural [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Integrative Microbiology of Zoonotic Agents [Paris and Montevideo] (IMiZA), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris] (IP), This work was funded by grants of the European Union (3to4) to V.G.M. and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy (EXC 2048/1, Project ID: 390686111 and EXC 1028, to V.G.M. and M.J.L., European Project: 289582,EC:FP7:KBBE,FP7-KBBE-2011-5,3TO4(2012), Universität zu Köln-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]-Max Planck Institute for Plant Breeding Research (MPIPZ), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur [Paris]
Subjects: 0106 biological sciences, 0301 basic medicine, Plant Science, Photosynthesis, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, Oxidoreductase, [CHIM.CRIS]Chemical Sciences/Cristallography, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], C4 photosynthesis, chemistry.chemical_classification, biology, RuBisCO, food and beverages, Metabolism, Amino acid, ddc:580, 030104 developmental biology, Enzyme, chemistry, Biochemistry, biology.protein, Nicotinamide adenine dinucleotide phosphate, 010606 plant biology & botany
Abstract: In C4 grasses of agronomical interest, malate shuttled into the bundle sheath cells is decarboxylated mainly by nicotinamide adenine dinucleotide phosphate (NADP)-malic enzyme (C4-NADP-ME). The activity of C4-NADP-ME was optimized by natural selection to efficiently deliver CO2 to Rubisco. During its evolution from a plastidic non-photosynthetic NADP-ME, C4-NADP-ME acquired increased catalytic efficiency, tetrameric structure and pH-dependent inhibition by its substrate malate. Here, we identified specific amino acids important for these C4 adaptions based on strict differential conservation of amino acids, combined with solving the crystal structures of maize and sorghum C4-NADP-ME. Site-directed mutagenesis and struc-tural analyses show that Q503, L544 and E339 are involved in catalytic efficiency; E339 confers pH-dependent regulation by malate, F140 is critical for the stabilization of the oligomeric structure and the N-terminal region is involved in tetramerization. Together, the identified molecular adaptations form the basis for the efficient catalysis and regulation of one of the central biochemical steps in C4 metabolism
Published: 2019
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5. Flow-Induced Transitions of Red Blood Cell Shapes under Shear

Author: Gerhard Gompper, Luca Lanotte, Simon Mendez, Dmitry A. Fedosov, Johannes Mauer, Manouk Abkarian, Franck Nicoud, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre de Biochimie Structurale [Montpellier] (CBS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Forschungszentrum Jülich GmbH, and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Shear elasticity, Materials science, Erythrocytes, General Physics and Astronomy, 01 natural sciences, Models, Biological, 010305 fluids & plasmas, Plasma, Cytosol, 0103 physical sciences, medicine, ddc:550, Computer Simulation, Elasticity (economics), 010306 general physics, Cell Size, Erythrocyte Membrane, Mechanics, Microfluidic Analytical Techniques, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Elasticity, Shear rate, Red blood cell, medicine.anatomical_structure, Membrane, Shear (geology), Buckling, Shear flow, Shear Strength
Abstract: A recent study of red blood cells (RBCs) in shear flow [Lanotte et al., Proc. Natl. Acad. Sci. U.S.A. 113, 13289 (2016)PNASA60027-842410.1073/pnas.1608074113] has demonstrated that RBCs first tumble, then roll, transit to a rolling and tumbling stomatocyte, and finally attain polylobed shapes with increasing shear rate, when the viscosity contrast between cytosol and blood plasma is large enough. Using two different simulation techniques, we construct a state diagram of RBC shapes and dynamics in shear flow as a function of shear rate and viscosity contrast, which is also supported by microfluidic experiments. Furthermore, we illustrate the importance of RBC shear elasticity for its dynamics in flow and show that two different kinds of membrane buckling trigger the transition between subsequent RBC states.
Published: 2018
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6. Effect of spectrin network elasticity on the shapes of erythrocyte doublets

Author: Hoore, Masoud, Yaya, François, Podgorski, Thomas, Wagner, Christian, Gompper, Gerhard, Fedosov, Dmitry, DYnamique des Fluides COmplexes et Morphogénèse [Grenoble] (DYFCOM-LIPhy), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute of Complex Systems and Institute for Advanced Simulation, Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, and Institute of Complex Systems (ICS)
Subjects: Physique [G04] [Physique, chimie, mathématiques & sciences de la terre], Physics [G04] [Physical, chemical, mathematical & earth Sciences], hemic and immune systems, macromolecular substances, sense organs, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], circulatory and respiratory physiology
Abstract: International audience; Red blood cell (RBC) aggregates play an important role in determining blood rheology. RBCs in plasma or polymer solution interact attractively to form various shapes of RBC doublets, where the attractive interactions can be varied by changing the solution conditions. A systematic numerical study on RBC doublet formation is performed, which takes into account the shear elasticity of the RBC membrane due to the spectrin cytoskeleton, in addition to the membrane bending rigidity. RBC membranes are modeled by two-dimensional triangulated surfaces embedded into three dimensions. The phase space of RBC doublet shapes in a wide range of adhesion strengths, reduced volumes, and shear elasticities is obtained. The shear elasticity of the RBC membrane changes the doublet phases significantly. Experimental images of RBC doublets in different solutions show similar configurations. Furthermore, we show that rouleau formation is affected by the doublet structure.
Published: 2018

7. New Insights on Signal Propagation by Sensory Rhodopsin II/Transducer Complex

Author: Johann P. Klare, Petr Utrobin, Ivan Gushchin, Vitaly Polovinkin, Alina Remeeva, Valentin Borshchevskiy, Valentin Gordeliy, Martin Engelhard, Sergei Grudinin, Georg Büldt, Taras Balandin, Andrii Ishchenko, Ekaterina Round, Institute of Complex Systems (ICS), ICS-6: Structural Biochemistry ( ICS-6), Institute of Crystallography [Aachen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Max Planck Institute of Molecular Physiology, Max-Planck-Gesellschaft, Department of Physics, University of Osnabrück, Osnabrück University, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Universität Osnabrück - Osnabrück University
Subjects: Models, Molecular, 0301 basic medicine, Magnetic Resonance Spectroscopy, Protein Conformation, Archaeal Proteins, Static Electricity, Plasma protein binding, Biology, Article, HAMP domain, Structure-Activity Relationship, 03 medical and health sciences, Sensory Rhodopsins, Protein structure, Membrane proteins, Halobacteriaceae, Protein Interaction Domains and Motifs, Negative phototaxis, Binding Sites, Multidisciplinary, 030102 biochemistry & molecular biology, Nanocrystallography, Sensory rhodopsin II, biology.organism_classification, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, 3. Good health, 030104 developmental biology, Biochemistry, Domain (ring theory), Biophysics, ddc:000, Protein Multimerization, Protein Binding, Signal Transduction
Abstract: The complex of two membrane proteins, sensory rhodopsin II (NpSRII) with its cognate transducer (NpHtrII), mediates negative phototaxis in halobacteria N. pharaonis. Upon light activation NpSRII triggers a signal transduction chain homologous to the two-component system in eubacterial chemotaxis. Here we report on crystal structures of the ground and active M-state of the complex in the space group I212121. We demonstrate that the relative orientation of symmetrical parts of the dimer is parallel (“U”-shaped) contrary to the gusset-like (“V”-shaped) form of the previously reported structures of the NpSRII/NpHtrII complex in the space group P21212, although the structures of the monomers taken individually are nearly the same. Computer modeling of the HAMP domain in the obtained “V”- and “U”-shaped structures revealed that only the “U”-shaped conformation allows for tight interactions of the receptor with the HAMP domain. This is in line with existing data and supports biological relevance of the “U” shape in the ground state. We suggest that the “V”-shaped structure may correspond to the active state of the complex and transition from the “U” to the “V”-shape of the receptor-transducer complex can be involved in signal transduction from the receptor to the signaling domain of NpHtrII.
Published: 2017
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8. HermiteFit: fast-fitting atomic structures into a low-resolution density map using three-dimensional orthogonal Hermite functions

Author: Georgy Derevyanko, Sergei Grudinin, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), ANR-11-MONU-0006,PEPSI,Expansions Polynomiales de Structures de Protéines et Interactions(2011), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Hermite spline, Protein Conformation, Fast Fourier transform, Basis function, density fitting, Cubic Hermite spline, symbols.namesake, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Structural Biology, Hermite interpolation, HermiteFit, [CHIM.CRIS]Chemical Sciences/Cristallography, Cryo-EM, [INFO.INFO-MS]Computer Science [cs]/Mathematical Software [cs.MS], Mathematics, Crystallography, Hermite polynomials, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], spherical harmonics, Spherical harmonics, Chaperonin 60, General Medicine, fast Fourier transform, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Hermite orthogonal polynomials, Fourier transform, symbols, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Conotoxins, Algorithm, Algorithms
Abstract: HermiteFit, a novel algorithm for fitting a protein structure into a low-resolution electron-density map, is presented. The algorithm accelerates the rotation of the Fourier image of the electron density by using three-dimensional orthogonal Hermite functions. As part of the new method, an algorithm for the rotation of the density in the Hermite basis and an algorithm for the conversion of the expansion coefficients into the Fourier basis are presented.HermiteFitwas implemented using the cross-correlation or the Laplacian-filtered cross-correlation as the fitting criterion. It is demonstrated that in the Hermite basis the Laplacian filter has a particularly simple form. To assess the quality of density encoding in the Hermite basis, an analytical way of computing the crystallographicRfactor is presented. Finally, the algorithm is validated using two examples and its efficiency is compared with two widely used fitting methods,ADP_EMandcoloresfrom theSituspackage.HermiteFitwill be made available at http://nano-d.inrialpes.fr/software/HermiteFit or upon request from the authors.
Published: 2014
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9. Boron-Doped Nanocrystalline Diamond Microelectrode Arrays Monitor Cardiac Action Potentials

Author: Philippe Bergonzo, Andreas Offenhäusser, Vanessa Maybeck, Richard B. Jackman, Robert Edgington, Emanuel Scorsone, Alexandre Bongrain, Joseph O. Welch, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, University College of London [London] (UCL), Laboratoire Capteurs Diamant (LCD-LIST), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, European Project: FP6-NMP- 033345, Laboratoire d'Intégration des Systèmes et des Technologies (LIST), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST)
Subjects: Fabrication, Materials science, nanocrystalline diamond, Biomedical Engineering, Action Potentials, nanodiamond, Pharmaceutical Science, Nanotechnology, 02 engineering and technology, Substrate (electronics), engineering.material, 010402 general chemistry, 01 natural sciences, Cell Line, Biomaterials, biocompatibility, action potential, diamond, signal detection, sensor, Humans, boron doping, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Boron, instrumentation, Doping, Diamond, 021001 nanoscience & nanotechnology, diamond electrode, 0104 chemical sciences, Microelectrode, Interfacing, ddc:540, Electrode, engineering, 0210 nano-technology, Microelectrodes, diamond microelectrode array, Electrochemical window
Abstract: International audience; The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A non-reductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators.
Published: 2013
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10. Interfacing neurons on carbon nanotubes covered with diamond

Author: Silke Seyock, Lionel Rousseau, Clément Hébert, Emmanuel Scorsone, Andreas Offenhäusser, Philippe Bergonzo, Vanessa Maybeck, Gaelle Lissorgues, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Laboratoire Capteurs Diamant (LCD-LIST), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Electronique, Systèmes de communication et Microsystèmes (ESYCOM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris-Est Marne-la-Vallée (UPEM)-ESIEE Paris, Universitat Autònoma de Barcelona (UAB), European Project: 280433,EC:FP7:NMP,FP7-NMP-2011-SMALL-5,NEUROCARE(2012), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), and Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris-Est Marne-la-Vallée (UPEM)-ESIEE Paris
Subjects: NANOCRYSTALLINE DIAMOND, Cell viability, Scanning electron microscope, NANOFIBER, General Chemical Engineering, Nanotechnology, 02 engineering and technology, Carbon nanotube, Substrate (electronics), engineering.material, 010402 general chemistry, 01 natural sciences, Focused ion beam, BIOCOMPATIBILITY, law.invention, CELL-ADHESION PROPERTIES, [SPI.MAT]Engineering Sciences [physics]/Materials, Cell attachments, Electrode surfaces, CULTURE, law, Nano-crystalline diamonds, BORON-DOPED DIAMOND, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Single structure, Bioelectronics, TRANSMISSION ELECTRON-MICROSCOPY, NANOWIRE ARRAYS, Chemistry, SURFACES, Diamond, FUNCTIONALIZED DIAMOND, General Chemistry, 021001 nanoscience & nanotechnology, 0104 chemical sciences, [SPI.TRON]Engineering Sciences [physics]/Electronics, [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, Transmission electron microscopy, Chemical window, ddc:540, Electrode, engineering, Different heights, Neuronal cell, 0210 nano-technology
Abstract: International audience; A recently discovered material, carbon nanotubes covered with diamond (DCNTs) was tested for its suitability in bioelectronics applications. Diamond shows advantages for bioelectronics applications (wide electro chemical window and bioinertness). This study investigates the effect of electrode surface shape (flat or three dimensional) on cell growth and behavior. For comparison, flat nanocrystalline diamond substrates were used. Primary embryonic neurons were grown on top of the structures and neither incorporated the structures nor did they grow in between the single structures. The interface was closely examined using focused ion beam (FIB) and scanning electron microscopy. Of special interest was the interface between cell and substrate. 5% to 25% of the cell membrane adhered to the substrate, which fits the theoretical estimated value. While investigating the conformity of the neurons, it could be observed that the cell membrane attaches to different heights of the tips of the 3D structure. However, the aspect ratio of the structures had no effect on the cell viability. These results let us assume that not more than 25% of cell attachment is needed for the survival of a functional neuronal cell.
Published: 2017
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11. Active State of Sensory Rhodopsin II: Structural Determinants for Signal Transfer and Proton Pumping

Author: Martin Engelhard, Anastasia Reshetnyak, Valentin Gordeliy, Andrii Ishchenko, Sergei Grudinin, Valentin Borshchevskiy, Ekaterina Round, Ivan Gushchin, Georg Büldt, Moscow Institute of Physics and Technology [Moscow] (MIPT), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institute of Crystallography [Aachen], Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Molecular Physiology, Max-Planck-Gesellschaft, This work was supported by the program 'Chaires d'excellence' edition 2008 of ANR France, by a CEA(IBS)-HGF(FZJ) STC 5.1 specific agreement, and by a Marie Curie grant for the training and career development of researchers (FP7-PEOPLE- 2007-1-1-ITN, project SBMPs). This work was performed in the framework of Russian State contract numbers 02.740.11.0299, 02.740.11.5010, 974 (in the framework of activity 1.2.2), and P211 (in the framework of activity 1.3.2) of the Federal Target Program 'Scientific and academic research cadres of innovative Russia' for the years 2009- 2013., European Project: 211800,EC:FP7:PEOPLE,FP7-PEOPLE-2007-1-1-ITN,SBMPS(2008), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), and Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: Models, Molecular, Protein Folding, Archaeal Proteins, Natronobacterium, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Crystallography, X-Ray, Models, Biological, Signal, 03 medical and health sciences, Structural Biology, Sensory Rhodopsins, membrane protein, Molecular Biology, 030304 developmental biology, G protein-coupled receptor, 0303 health sciences, Halobacteriaceae, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, Chemistry, 030302 biochemistry & molecular biology, Sensory rhodopsin II, Proton Pumps, Carotenoids, Transmembrane protein, Protein Structure, Tertiary, Transport protein, Crystallography, active state, Rhodopsin, Biophysics, biology.protein, Bacterial rhodopsins, Signal transduction, Crystallization, signaling, Signal Transduction, bacterial rhodopsins
Abstract: International audience; The molecular mechanism of transmembrane signal transduction is still a pertinent question in cellular biology. Generally, a receptor can transfer an external signal via its cytoplasmic surface as found for GPCRs like rhodopsin or via the membrane domain like it is utilized by sensory rhodopsin II (SRII) in complex with its transducer HtrII. In the absence of HtrII SRII functions as a proton pump. Here, we report on the crystal structure of the active state of SRII from Natronomonas pharaonis (NpSRII). The problem of a dramatic loss of the diffraction quality upon loading of the active state was overcome by growing better crystals and reducing the occupancy of the state. The determined conformational changes at the region comprising helices F and G are similar to those observed for the NpSRII-transducer complex but they are much more pronounced. Meaning of these differences for proton pumping ability and understanding of the signal transduction by NpSRII is discussed.
Published: 2011
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12. Crystal structure of a light-driven sodium pump

Author: Gushchin, Ivan Yu., Shevchenko, Vitaly, Polovinkin, Vitaly, Kovalev, Kirill, Alekseev, Alexey, Round, Ekaterina, Borshchevskiy, Valentin, Balandin, Taras, Popov, Alexander, Gensch, Thomas, Fahlke, Christoph, Bamann, Christian, Willbold, Dieter, Büldt, Georg, Bamberg, Ernst, Gordeliy, Valentin I., Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Moscow Institute of Physics and Technology [Moscow] (MIPT), laboratoire d'archéologie, Université de Yakutsk, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Biophysical Chemistry, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Helmholtz-Gemeinschaft = Helmholtz Association, Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Thomas, Frank
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

13. Structural and Functional Investigation of Flavin Binding Center of the NqrC Subunit of Sodium-Translocating NADH:Quinone Oxidoreductase from Vibrio harveyi

Author: Galina S. Kachalova, Alexander Popov, Ekaterina Round, Kirill Kovalev, Vitaly Polovinkin, Alexey Mishin, Valentin Gordeliy, Alexander V. Bogachev, Ivan Gushchin, Valentin Borshchevskiy, Andrii Ishchenko, Yulia V. Bertsova, Moscow Institute of Physics and Technology [Moscow] (MIPT), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University (MSU), Moscow Inst Phys & Technol, Lab Adv Studies Membrane Prot, Dolgoprudnyi, Russia, A.N. Bach Institute of Biochemistry, Russian Academy of Sciences [Moscow] (RAS), European Synchrotron Radiation Facility (ESRF), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Forschungszentrum Jülich GmbH, Institut de biologie structurale [1992-2019] (IBS - UMR 5075 [1992-2019]), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: animal structures, Stereochemistry, Flavin Mononucleotide, [SDV]Life Sciences [q-bio], Recombinant Fusion Proteins, Molecular Sequence Data, Respiratory chain, lcsh:Medicine, Flavin mononucleotide, Flavin group, Calorimetry, Molecular Dynamics Simulation, Quinone oxidoreductase, Crystallography, X-Ray, Cofactor, chemistry.chemical_compound, Protein structure, Quinone Reductases, Bacterial Proteins, Oxidoreductase, Amino Acid Sequence, lcsh:Science, Vibrio, chemistry.chemical_classification, Multidisciplinary, Binding Sites, biology, lcsh:R, Protein Structure, Tertiary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Protein Subunits, chemistry, Biochemistry, biology.protein, lcsh:Q, ddc:500, Sequence Alignment, Research Article, Protein Binding
Abstract: International audience; Na +-translocating NADH:quinone oxidoreductase (NQR) is a redox-driven sodium pump operating in the respiratory chain of various bacteria, including pathogenic species. The enzyme has a unique set of redox active prosthetic groups, which includes two covalently bound flavin mononucleotide (FMN) residues attached to threonine residues in subunits NqrB and NqrC. The reason of FMN covalent bonding in the subunits has not been established yet. In the current work, binding of free FMN to the apo-form of NqrC from Vibrio har-veyi was studied showing very low affinity of NqrC to FMN in the absence of its covalent bonding. To study structural aspects of flavin binding in NqrC, its holo-form was crystallized and its 3D structure was solved at 1.56 Å resolution. It was found that the isoalloxazine moi-ety of the FMN residue is buried in a hydrophobic cavity and that its pyrimidine ring is squeezed between hydrophobic amino acid residues while its benzene ring is extended from the protein surroundings. This structure of the flavin-binding pocket appears to provide flexibility of the benzene ring, which can help the FMN residue to take the bended conforma-tion and thus to stabilize the one-electron reduced form of the prosthetic group. These properties may also lead to relatively weak noncovalent binding of the flavin. This fact along with periplasmic location of the FMN-binding domains in the vast majority of NqrC-like proteins may explain the necessity of the covalent bonding of this prosthetic group to prevent its loss to the external medium.
Published: 2015
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14. Structure of the light-driven sodium pump KR2 and its implications for optogenetics

Author: Pavel Buslaev, Valentin Gordeliy, Vitaly Polovinkin, Vitaly Shevchenko, Ivan Gushchin, Ernst Bamberg, Valentin Borshchevskiy, Thomas, Frank, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Max Planck Institute of Biophysics [Frankfurt am Main] (MPIBP), Max-Planck-Gesellschaft, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Models, Molecular, 0301 basic medicine, Light, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Sodium-Potassium-Exchanging ATPase, Sodium, chemistry.chemical_element, Optogenetics, Crystallography, X-Ray, Protein Engineering, Biochemistry, Protein Structure, Secondary, Ion, 03 medical and health sciences, Na+/K+-ATPase, Binding site, Molecular Biology, Ion transporter, ComputingMilieux_MISCELLANEOUS, Binding Sites, Ion Transport, Photolysis, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Cell Biology, Protein engineering, Protein Structure, Tertiary, Crystallography, 030104 developmental biology, Models, Chemical, Mutation, Biophysics, Protein Multimerization
Abstract: A key and common process present in organisms from all domains of life is the maintenance of the ion gradient between the inside and the outside of the cell. The gradient is generated by various active transporters, among which are the light-driven ion pumps of the microbial rhodopsin family. Whereas the proton-pumping and anion-pumping rhodopsins have been known for a long time, the cation (sodium) pumps were described only recently. Following the discovery, high-resolution atomic structures of the pump KR2 were determined that revealed the complete ion translocation pathway, including the positions of the characteristic Asn-Asp-Gln (NDQ) triad, the unusual ion uptake cavity acting as a selectivity filter, the unique N-terminal α-helix, capping the ion release cavity, and unexpected flexibility of the retinal-binding pocket. The structures also revealed pentamerization of KR2 and binding of sodium ions at the interface. Finally, on the basis of the structures, potassium-pumping KR2 variants have been designed, making the findings even more important for optogenetic applications. In this Structural Snapshot, we analyse the implications of the structural findings for understanding the sodium translocation mechanism and application of the pump and its mutants in optogenetics.
Published: 2015

15. An Approach to Heterologous Expression of Membrane Proteins. The Case of Bacteriorhodopsin

Author: Bratanov, Dmitry, Balandin, Taras, Round, Ekaterina, Shevchenko, Vitaly, Gushchin, Ivan Yu., Polovinkin, Vitaly, Borshchevskiy, Valentin, Gordeliy, Valentin I., Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Thomas, Frank
Subjects: Halobacterium salinarum, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Sequence Data, lcsh:R, lcsh:Medicine, Crystallography, X-Ray, Recombinant Proteins, Protein Structure, Tertiary, Bacteriorhodopsins, Escherichia coli, Mutagenesis, Site-Directed, Nucleic Acid Conformation, lcsh:Q, Amino Acid Sequence, RNA, Messenger, ddc:500, lcsh:Science, Sequence Alignment, Research Article
Abstract: International audience; Heterologous overexpression of functional membrane proteins is a major bottleneck of structural biology. Bacteriorhodopsin from Halobium salinarum (bR) is a striking example of the difficulties in membrane protein overexpression. We suggest a general approach with a finite number of steps which allows one to localize the underlying problem of poor expression of a membrane protein using bR as an example. Our approach is based on constructing chimeric proteins comprising parts of a protein of interest and complementary parts of a homologous protein demonstrating advantageous expression. This complementary protein approach allowed us to increase bR expression by two orders of magnitude through the introduction of two silent mutations into bR coding DNA. For the first time the high quality crystals of bR expressed in E. Coli were obtained using the produced protein. The crystals obtained with in meso nanovolume crystallization diffracted to 1.67 Å.
Published: 2015
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16. X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism

Author: Przemyslaw Nogly, Andrii Ishchenko, Ana M. Esteves, Nuno Borges, Margarida Archer, Ekaterina Round, Isabel Moraes, Valentin Gordeliy, Alina Remeeva, Ivan Gushchin, Sergei Grudinin, Valentin Borshchevskiy, Pikyee Ma, Helena Santos, Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institute of Crystallography [Aachen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Department of Life Sciences, Imperial College London, Membrane Protein Laboratory, Diamond Light Source, DIAMOND Light source, STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), and Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Stereochemistry, Protein-protein interactions, Archaeal Proteins, Molecular Sequence Data, General Physics and Astronomy, membrane proteins, Crystallography, X-Ray, Cytidine Diphosphate, Protein Structure, Secondary, General Biochemistry, Genetics and Molecular Biology, Conserved sequence, Cell membrane, Phosphotransferase, Catalytic Domain, medicine, Magnesium, Amino Acid Sequence, Integral membrane protein, Magnesium ion, Multidisciplinary, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Cell Membrane, Phosphotransferases, Active site, General Chemistry, Transmembrane protein, Protein Structure, Tertiary, medicine.anatomical_structure, Membrane protein, Biochemistry, Archaeoglobus fulgidus, Biocatalysis, biology.protein, lipids (amino acids, peptides, and proteins), ddc:500, Sequence Alignment
Abstract: International audience; Phospholipids have major roles in the structure and function of all cell membranes. Most integral membrane proteins from the large CDP-alcohol phosphatidyltransferase family are involved in phospholipid biosynthesis across the three domains of life. They share a conserved sequence pattern and catalyse the displacement of CMP from a CDP-alcohol by a second alcohol. Here we report the crystal structure of a bifunctional enzyme comprising a cytoplasmic nucleotidyltransferase domain (IPCT) fused with a membrane CDP-alcohol phosphotransferase domain (DIPPS) at 2.65 Å resolution. The bifunctional protein dimerizes through the DIPPS domains, each comprising six transmembrane α-helices. The active site cavity is hydrophilic and widely open to the cytoplasm with a magnesium ion surrounded by four highly conserved aspartate residues from helices TM2 and TM3. We show that magnesium is essential for the enzymatic activity and is involved in catalysis. Substrates docking is validated by mutagenesis studies, and a structure-based catalytic mechanism is proposed.
Published: 2014
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17. Crystal structure of Escherichia coli-expressed Haloarcula marismortui bacteriorhodopsin I in the trimeric form

Author: Shevchenko, Vitaly, Gushchin, Ivan, Polovinkin, V., Round, E., Borshchevskiy, Valentin, Utrobin, P., Popov, A., Balandin, Taras, Büldt, Georg, Gordeliy, Valentin, Moscow Inst Phys & Technol, Lab Adv Studies Membrane Prot, Dolgoprudnyi, Russia, Res Ctr Julich GmbH, Inst Complex Syst ICS Struct Biochem 6, Julich, Germany, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Haloarcula marismortui, Membrane Protein Complexes, [SDV]Life Sciences [q-bio], Cell Membranes, Biophysics, lcsh:Medicine, Industrial Processes, Research and Analysis Methods, Crystallography, X-Ray, Biochemistry, Protein Structure, Secondary, Industrial Engineering, Escherichia coli, lcsh:Science, Ion Transport, lcsh:R, Biology and Life Sciences, Proteins, Protein Complexes, Membrane Proteins, Water, Hydrogen Bonding, Cell Biology, Crystallization Techniques, Lipids, Membrane Protein Crystallization, Macromolecular Crystallography, Transmembrane Proteins, Separation Processes, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Bacteriorhodopsins, Crystallographic Techniques, Engineering and Technology, lcsh:Q, ddc:500, Cellular Structures and Organelles, Protein Multimerization, Hydrophobic and Hydrophilic Interactions, Research Article
Abstract: International audience; Bacteriorhodopsins are a large family of seven-helical transmembrane proteins that function as light-driven proton pumps. Here, we present the crystal structure of a new member of the family, Haloarcula marismortui bacteriorhodopsin I (HmBRI) D94N mutant, at the resolution of 2.5 angstrom. While the HmBRI retinal-binding pocket and proton donor site are similar to those of other archaeal proton pumps, its proton release region is extended and contains additional water molecules. The protein's fold is reinforced by three novel inter-helical hydrogen bonds, two of which result from double substitutions relative to Halobacterium salinarum bacteriorhodopsin and other similar proteins. Despite the expression in Escherichia coli and consequent absence of native lipids, the protein assembles as a trimer in crystals. The unique extended loop between the helices D and E of HmBRI makes contacts with the adjacent protomer and appears to stabilize the interface. Many lipidic hydrophobic tail groups are discernible in the membrane region, and their positions are similar to those of archaeal isoprenoid lipids in the crystals of other proton pumps, isolated from native or native-like sources. All these features might explain the HmBRI properties and establish the protein as a novel model for the microbial rhodopsin proton pumping studies
Published: 2014
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18. Ground state structure of D75N mutant of sensory rhodopsin II in complex with its cognate transducer

Author: Johann P. Klare, Taras Balandin, Valentin Gordeliy, Martin Engelhard, Andrii Ishchenko, Ekaterina Round, Valentin Borshchevskiy, Alina Remeeva, Sergei Grudinin, Ivan Gushchin, Georg Büldt, Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Institute of Crystallography [Aachen], Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Moscow Institute of Physics and Technology [Moscow] (MIPT), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Fachbereich Physik [Osnabrück], Universität Osnabrück - Osnabrück University, Max Planck Institute of Molecular Physiology, Max-Planck-Gesellschaft, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), and Universitat Osnabruck
Subjects: Models, Molecular, Light, Archaeal Proteins, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Mutant, Biophysics, Biology, Crystallography, X-Ray, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Rhodopsins, Microbial, Aspartic acid, medicine, Sensory Rhodopsins, Radiology, Nuclear Medicine and imaging, membrane protein, x-ray crystallography, 030304 developmental biology, Negative phototaxis, 0303 health sciences, Mutation, Halobacteriaceae, Radiation, Radiological and Ultrasound Technology, Intracellular Signaling Peptides and Proteins, Sensory rhodopsin II, Hydrogen Bonding, Chemotaxis, Carotenoids, Two-component regulatory system, Biochemistry, Multiprotein Complexes, retinal protein, Signal transduction, Halorhodopsins, 030217 neurology & neurosurgery, signal transduction
Abstract: International audience; The complex of sensory rhodopsin II (NpSRII) with its cognate transducer (NpHtrII) mediates negative phototaxis in halobacteria Natronomonas pharaonis. Upon light activation NpSRII triggers, by means of NpHtrII, a signal transduction chain homologous to the two component system in eubacterial chemotaxis. Here we report on the crystal structure of the ground state of the mutant NpSRII-D75N/NpHtrII complex in the space group I212121. Mutations of this aspartic acid in light-driven proton pumps dramatically modify or/and inhibit protein functions. However, in vivo studies show that the similar D75N mutation retains functionality of the NpSRII/NpHtrII complex. The structure provides the molecular basis for the explanation of the unexpected observation that the wild and the mutant complexes display identical physiological response on light excitation.
Published: 2013
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19. Two Distinct States of the HAMP Domain from Sensory Rhodopsin Transducer Observed in Unbiased Molecular Dynamics Simulations

Author: Ivan Gushchin, Sergei Grudinin, Valentin Gordeliy, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Moscow Institute of Physics and Technology [Moscow] (MIPT), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: MESH: Signal Transduction, Molecular dynamics simulations Signal transduction Eigenvector analysis, lcsh:Medicine, MESH: Protein Structure, Secondary, Molecular Dynamics, Biochemistry, Biophysics Simulations, Protein Structure, Secondary, HAMP domain, Molecular dynamics, MESH: Protein Structure, Tertiary, Protein structure, Computational Chemistry, Molecular Cell Biology, Phototaxis, Biochemical Simulations, Halobacteriaceae, Signaling in Cellular Processes, Membrane Receptor Signaling, MESH: Molecular Dynamics Simulation, lcsh:Science, Biochemistry Simulations, 0303 health sciences, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030302 biochemistry & molecular biology, MESH: Hydrophobic and Hydrophilic Interactions, MESH: Archaeal Proteins, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Chemistry, Rhodopsin, Biophysic Al Simulations, ddc:500, Transmembrane Signaling, Hydrophobic and Hydrophilic Interactions, Signal Transduction, Research Article, Protein family, Archaeal Proteins, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Biophysics, Biology, Molecular Dynamics Simulation, Turn (biochemistry), 03 medical and health sciences, MESH: Halobacteriaceae, Sensory Rhodopsins, 030304 developmental biology, MESH: Sensory Rhodopsins, lcsh:R, Computational Biology, biology.organism_classification, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Protein Structure, Tertiary, biology.protein, lcsh:Q, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; HAMP domain is a ubiquitous module of bacterial and archaeal two-component signaling systems. Considerable progress has been made recently in studies of its structure and conformational changes. However, the mechanism of signal transduction through the HAMP domain is not clear. It remains a question whether all the HAMPs have the same mechanism of action and what are the differences between the domains from different protein families. Here, we present the results of unbiased molecular dynamics simulations of the HAMP domain from the archaeal phototaxis signal transducer NpHtrII. Two distinct conformational states of the HAMP domain are observed, that differ in relative position of the helices AS1 and AS2. The longitudinal shift is roughly equal to a half of an alpha-helix turn, although sometimes it reaches one full turn. The states are closely related to the position of bulky hydrophobic aminoacids at the HAMP domain core. The observed features are in good agreement with recent experimental results and allow us to propose that the states detected in the simulations are the resting state and the signaling state of the NpHtrII HAMP domain. To the best of our knowledge, this is the first observation of the same HAMP domain in different conformations. The simulations also underline the difference between AMBER ff99-SB-ILDN and CHARMM22-CMAP forcefields, as the former favors the resting state and the latter favors the signaling state
Published: 2013
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20. A Novel Dimerization Interface of Cyclic Nucleotide Binding Domain, which is Disrupted in Presence of cAMP: Implications for CNG Channels Gating

Author: Ivan Yu. Gushchin, Valentin Gordeliy, Sergei Grudinin, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Program 'Chaires d'excellence' edition 2008 of ANR France, CEA(IBS) - HGF(FZJ) STC 5.1 specific agreement, the MC grant for training and career development of researchers (Marie Curie, FP7-PEOPLE-2007-1-1-ITN, project SBMPs), EC FP7 grant for the EDICT consortium (HEALTH-201924). This work was done in the framework of Russian State Contracts № 02.740.11.0299, № 02.740.11.5010 and №P974 in the framework of activity 1.2.2 of the Federal Target Program 'Scientific and academic research cadres of innovative Russia' for 2009-2013 years. Part of this work was supported by the German Federal Ministry of Education and Research (PhoNa - Photonic Nanomaterials). Partial financial support from ONEXIM group is gratefully aknowledged. Part of the simulations was conducted on the JUROPA supercomputer at Forschungszentrum Juelich., Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)
Subjects: Guanine, channel gating, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cyclic Nucleotide-Gated Cation Channels, cyclic-nucleotide binding domain, Gating, Molecular Dynamics Simulation, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Cyclic nucleotide, chemistry.chemical_compound, Molecular dynamics, 0302 clinical medicine, Epac2, Cyclic AMP, Guanine Nucleotide Exchange Factors, Physical and Theoretical Chemistry, Cyclic nucleotide-gated ion channel, Amino Acids, 030304 developmental biology, 0303 health sciences, Cyclic-nucleotide binding domain, Principal Component Analysis, Effector, Organic Chemistry, CNG channel, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Computer Science Applications, Protein Structure, Tertiary, Computational Theory and Mathematics, chemistry, Biochemistry, Cyclic nucleotide-binding domain, ddc:540, Biophysics, CAMP binding, Protein Multimerization, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Channel gating, Ion Channel Gating, 030217 neurology & neurosurgery, Protein Binding
Abstract: International audience; Cyclic nucleotide binding domain (CNBD) is a ubiquitous domain of effector proteins involved in signalling cascades of prokaryota and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in case of several proteins. However, this knowledge is hardly applicable to cNMP-modulated cation channels. Despite the availability of CNBD crystal structures of bacterial cyclic nucleotide-gated (CNG) and mammalian hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels in presence and absence of the cNMP, the full understanding of CNBD conformational changes during activation is lacking. Here, we describe a novel CNBD dimerization interface found in crystal structures of bacterial CNG channel MlotiK1 and mammalian cAMP-activated guanine nucleotide-exchange factor Epac2. Molecular dynamics simulations show that the found interface is stable on the studied timescale of 100 ns, in contrast to the dimerization interface, reported previously. Comparisons with cN-bound structures of CNBD show that the dimerization is incompatible with cAMP binding. Thus, the cAMP-dependent monomerization of CNBD may be an alternative mechanism of the cAMP sensing. Based on these findings, we propose a model of the bacterial CNG channel modulation by cAMP.
Published: 2012
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21. Role of the HAMP Domain Region of Sensory Rhodopsin Transducers in Signal Transduction

Author: Valentin Gordeliy, Sergei Grudinin, Ivan Gushchin, Moscow Institute of Physics and Technology [Moscow] (MIPT), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), This work was supported by the program 'Chaires d'excellence' edition 2008 of ANR France, CEA(IBS)-HGF(FZJ) STC 5.1 specific agreement, the MC grant for training and career development of researchers (Marie Curie, FP7-PEOPLE-2007-1-1-ITN, project SBMPs), and an EC FP7 grant for the EDICT consortium (HEALTH-201924). This work was conducted in the framework of Russian State Contracts 02.740.11.0299, 02.740.11.5010, and P974 in the framework of activity 1.2.2 of the Federal Target Program 'Scientific and academic research cadres of innovative Russia' for 2009−2013., Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cytoplasm, Histidine Kinase, chemistry [Protein Kinases], Cytoplasmic part, Biochemistry, Protein Structure, Secondary, HAMP domain, 0302 clinical medicine, Sensory Rhodopsins, enzymology [Cytoplasm], physiology [Phosphoric Monoester Hydrolases], Coiled coil, 0303 health sciences, Halobacteriaceae, physiology [Light Signal Transduction], biology, metabolism [Halobacteriaceae], [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Transmembrane domain, Rhodopsin, HAMP, Adenylyl Cyclases, physiology [Sensory Rhodopsins], Adenylate Cyclase, Light Signal Transduction, chemistry [Bacterial Proteins], physiology [Cytoplasm], Archaeal Proteins, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], physiology [Protein Kinases], HtrII protein, Natronobacterium pharaonis, Methyl-Accepting Chemotaxis Proteins, 03 medical and health sciences, Bacterial Proteins, ddc:570, chemistry [Membrane Proteins], chemistry [Phosphoric Monoester Hydrolases], Kinase activity, physiology [Bacterial Proteins], physiology [Adenylate Cyclase], metabolism [Cytoplasm], 030304 developmental biology, physiology [Archaeal Proteins], physiology [Membrane Proteins], chemistry [Protein Subunits], Membrane Proteins, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Phosphoric Monoester Hydrolases, Protein Structure, Tertiary, chemistry [Archaeal Proteins], Crystallography, Protein Subunits, protein-histidine kinase, biology.protein, Biophysics, chemistry [Adenylate Cyclase], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], enzymology [Halobacteriaceae], methyl-accepting chemotaxis proteins, Protein Kinases, 030217 neurology & neurosurgery, chemistry [Sensory Rhodopsins]
Abstract: International audience; Archaea are able to sense light via the complexes of sensory rhodopsins I and II and their corresponding chemoreceptor-like transducers HtrI and HtrII. Though generation of the signal has been studied in detail, the mechanism of its propagation to the cytoplasm remains obscured. The cytoplasmic part of the transducer consists of adaptation and kinase activity modulating regions, connected to transmembrane helices via two HAMP (histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis proteins, phosphatases) domains. The inter-HAMP region of Natronomonas pharaonis HtrII (NpHtrII) was found to be α-helical [Hayashi, K., et al. (2007) Biochemistry 46, 14380−14390]. We studied the inter-HAMP regions of NpHtrII and other phototactic signal transducers by means of molecular dynamics. Their structure is found to be a bistable asymmetric coiled coil, in which the protomers are longitudinally shifted by 1.3 Å. The free energy penalty for the symmetric structure is estimated to be 1.2−1.5 kcal/mol depending on the molarity of the solvent. Both flanking HAMP domains are mechanistically coupled to the inter-HAMP region and are asymmetric. The longitudinal shift in the inter-HAMP region is coupled with the in-plane displacement of the cytoplasmic part by 8.6 Å relative to the transmembrane part. The established properties suggest that (1) the signal may be transduced through the inter-HAMP domain switching and (2) the inter-HAMP region may allow cytoplasmic parts of the transducers to come sufficiently close to each other to form oligomers.
Published: 2010
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22. Outcome of the First wwPDB Hybrid/Integrative Methods Task Force Workshop

Author: Marc A. Marti-Renom, John D. Westbrook, Eldon L. Ulrich, Wah Chiu, Randy J. Read, Catherine L. Lawson, Ruth Nussinov, Kay Grünewald, Gerhard Hummer, Aleksandras Gutmanas, Ardan Patwardhan, Maya Topf, Matteo Dal Peraro, Frank Di Maio, Gerard J. Kleywegt, Paul D. Adams, Claus A. M. Seidel, Jill Trewhella, Thomas E. Ferrin, Jens Meiler, Kenji Iwasaki, Andrej Sali, Michael Nilges, Richard Henderson, Alexandre M. J. J. Bonvin, Helen M. Berman, Graham T. Johnson, Helen R. Saibil, Haruki Nakamura, Stephen K. Burley, Gunnar F. Schröder, John L. Markley, Torsten Schwede, Dmitri I. Svergun, Sameer Velankar, Charles D. Schwieters, Gaetano T. Montelione, Juri Rappsilber, Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] (UCSF), University of California-University of California, Research Collaboratory for Structural Bioinformatics Protein Data Bank, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers)-Rutgers University System (Rutgers)-Center for Integrative Proteomics Research, School of Molecular and Microbial Biosciences, The University of Sydney, Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Skaggs School of Pharmacy and Pharmaceutical Sciences and San Diego Supercomputer Center, University of California [San Diego] (UC San Diego), BioMagResBank, Department of Biochemistry, University of Wisconsin-Madison, Institute for Protein Research [Osaka], Osaka University [Osaka], Physical Biosciences Division [LBNL Berkeley], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Department of Bioengineering, Bijvoet Center for Biomolecular Research [Utrecht], Utrecht University [Utrecht], National Center for Environmental Assessment, US Environmental Protection Agency (EPA), National Center for Macromolecular Imaging, Baylor College of Medecine, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Biochemistry [Washington ], University of Washington [Seattle], Division of Structural Biology, Wellcome Trust Centre of Human Genetics, University of Oxford, Laboratory of Molecular Biology [Cambridge], Medical Research Council, Department of Theoretical Biophysics [Frankfurt am Main], Max-Planck-Institut für Biophysik - Max Planck Institute of Biophysics (MPIBP), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Gene Regulation, Stem Cells and Cancer Program, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Department of Biochemistry, Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Bioinformatique structurale - Structural Bioinformatics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick National Laboratory for Cancer Research (FNLCR), Department of Human Molecular Genetics and Biochemistry, Tel Aviv University [Tel Aviv], Wellcome Trust Centre for Cell Biology, University of Edinburgh, Department of Bioanalytics, Technische Universität Berlin (TU), Department of Haematology, University of Cambridge [UK] (CAM), Department of Biological Sciences, Birkbeck College [University of London]-Institute of Structural and Molecular Biology (ISMB), Institute of Complex Systems (ICS), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Physics Department [Düsseldorf], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Division of Computational Bioscience, National Institutes of Health, Chair for Molecular Physical Chemistry, The workshop was supported by funding to PDBe by Wellcome Trust 088944, RCSB PDB by NSF DBI 1338415, PDBj by JST-NBDC, BMRB by NLM P41 LM05799, EMDataBank by NIH GM079429, and tax-deductible donations made to the wwPDB Foundation in support of wwPDB outreach activities., Sub NMR Spectroscopy, NMR Spectroscopy, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Tel Aviv University (TAU), and Technical University of Berlin / Technische Universität Berlin (TU)
Subjects: Models, Molecular, Computer science, Protein Conformation, Advisory Committees, Biophysics, Computational biology, Outcome (game theory), Biologia computacional, Article, Databases, 03 medical and health sciences, 0302 clinical medicine, Models, Structural Biology, Information and Computing Sciences, Taverne, Humans, Databases, Protein, Biological sciences, Molecular Biology, 030304 developmental biology, 0303 health sciences, Integrative bioinformatics, Extramural, Task force, Protein, Molecular, Experimental data, Computational Biology, Proteins, Biological Sciences, Data science, Visualization, Chemical Sciences, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Proteïnes, 030217 neurology & neurosurgery
Abstract: Structures of biomolecular systems are increasingly computed by integrative modeling that relies on varied types of experimental data and theoretical information. We describe here the proceedings and conclusions from the first wwPDB Hybrid/Integrative Methods Task Force Workshop held at the European Bioinformatics Institute in Hinxton, UK, on October 6 and 7, 2014. At the workshop, experts in various experimental fields of structural biology, experts in integrative modeling and visualization, and experts in data archiving addressed a series of questions central to the future of structural biology. How should integrative models be represented? How should the data and integrative models be validated? What data should be archived? How should the data and models be archived? What information should accompany the publication of integrative models? The workshop was supported by funding to PDBe by Wellcome Trust 088944; RCSB PDB by NSF DBI 1338415; PDBj by JST-NBDC; BMRB by NLM P41 LM05799; EMDataBank by NIH GM079429; and tax-deductible donations made to the wwPDB Foundation in support of wwPDB outreach activities.
Published: 2015
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23. Unusual features of the c-ring of F 1 F O ATP synthases.

Author: Vlasov AV, Kovalev KV, Marx SH, Round ES, Gushchin IY, Polovinkin VA, Tsoy NM, Okhrimenko IS, Borshchevskiy VI, Büldt GD, Ryzhykau YL, Rogachev AV, Chupin VV, Kuklin AI, Dencher NA, and Gordeliy VI
Subjects: Adenosine Triphosphate biosynthesis, Chloroplasts enzymology, Coenzymes metabolism, Crystallography, X-Ray, Mitochondrial Proton-Translocating ATPases metabolism, Models, Molecular, Plant Proteins metabolism, Protein Conformation, Protein Subunits metabolism, Spinacia oleracea enzymology, Ubiquinone metabolism, Mitochondrial Proton-Translocating ATPases ultrastructure, Plant Proteins ultrastructure, Protein Structure, Quaternary
Abstract: Membrane integral ATP synthases produce adenosine triphosphate, the universal "energy currency" of most organisms. However, important details of proton driven energy conversion are still unknown. We present the first high-resolution structure (2.3 Å) of the in meso crystallized c-ring of 14 subunits from spinach chloroplasts. The structure reveals molecular mechanisms of intersubunit contacts in the c 14 -ring, and it shows additional electron densities inside the c-ring which form circles parallel to the membrane plane. Similar densities were found in all known high-resolution structures of c-rings of F 1 F O ATP synthases from archaea and bacteria to eukaryotes. The densities might originate from isoprenoid quinones (such as coenzyme Q in mitochondria and plastoquinone in chloroplasts) that is consistent with differential UV-Vis spectroscopy of the c-ring samples, unusually large distance between polar/apolar interfaces inside the c-ring and universality among different species. Although additional experiments are required to verify this hypothesis, coenzyme Q and its analogues known as electron carriers of bioenergetic chains may be universal cofactors of ATP synthases, stabilizing c-ring and prevent ion leakage through it.
Published: 2019
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24. Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors.

Author: Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy É, Longpré JM, Ishchenko A, Popov P, Patel N, Fujimoto T, Maruyama T, Stauch B, Ergasheva M, Romanovskaia D, Stepko A, Kovalev K, Shevtsov M, Gordeliy V, Han GW, Katritch V, Borshchevskiy V, Sarret P, Mishin A, and Cherezov V
Subjects: Animals, Asthma genetics, Asthma metabolism, Computer Simulation, Crystallography, X-Ray, HEK293 Cells, Humans, Leukotriene D4 metabolism, Ligands, Models, Molecular, Molecular Docking Simulation, Mutagenesis, Protein Conformation, Protein Engineering, Receptors, Leukotriene drug effects, Sf9 Cells, Mutation, Receptors, Leukotriene chemistry, Receptors, Leukotriene genetics
Abstract: Cysteinyl leukotriene G protein-coupled receptors CysLT 1 and CysLT 2 regulate pro-inflammatory responses associated with allergic disorders. While selective inhibition of CysLT 1 R has been used for treating asthma and associated diseases for over two decades, CysLT 2 R has recently started to emerge as a potential drug target against atopic asthma, brain injury and central nervous system disorders, as well as several types of cancer. Here, we describe four crystal structures of CysLT 2 R in complex with three dual CysLT 1 R/CysLT 2 R antagonists. The reported structures together with the results of comprehensive mutagenesis and computer modeling studies shed light on molecular determinants of CysLTR ligand selectivity and specific effects of disease-related single nucleotide variants.
Published: 2019
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25. Unique structure and function of viral rhodopsins.

Author: Bratanov D, Kovalev K, Machtens JP, Astashkin R, Chizhov I, Soloviov D, Volkov D, Polovinkin V, Zabelskii D, Mager T, Gushchin I, Rokitskaya T, Antonenko Y, Alekseev A, Shevchenko V, Yutin N, Rosselli R, Baeken C, Borshchevskiy V, Bourenkov G, Popov A, Balandin T, Büldt G, Manstein DJ, Rodriguez-Valera F, Fahlke C, Bamberg E, Koonin E, and Gordeliy V
Subjects: Bacteriorhodopsins, Crystallography, X-Ray, Halobacterium salinarum, Ion Channel Gating, Ion Channels, Light, Molecular Dynamics Simulation, Protein Structure, Quaternary, Protein Structure, Tertiary, Rhodopsins, Microbial physiology, Phycodnaviridae metabolism, Rhodopsins, Microbial metabolism, Rhodopsins, Microbial ultrastructure
Abstract: Recently, two groups of rhodopsin genes were identified in large double-stranded DNA viruses. The structure and function of viral rhodopsins are unknown. We present functional characterization and high-resolution structure of an Organic Lake Phycodnavirus rhodopsin II (OLPVRII) of group 2. It forms a pentamer, with a symmetrical, bottle-like central channel with the narrow vestibule in the cytoplasmic part covered by a ring of 5 arginines, whereas 5 phenylalanines form a hydrophobic barrier in its exit. The proton donor E42 is placed in the helix B. The structure is unique among the known rhodopsins. Structural and functional data and molecular dynamics suggest that OLPVRII might be a light-gated pentameric ion channel analogous to pentameric ligand-gated ion channels, however, future patch clamp experiments should prove this directly. The data shed light on a fundamentally distinct branch of rhodopsins and may contribute to the understanding of virus-host interactions in ecologically important marine protists.
Published: 2019
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26. Small-angle neutron and X-ray scattering analysis of the supramolecular organization of rhodopsin in photoreceptor membrane.

Author: Feldman TB, Ivankov OI, Kuklin AI, Murugova TN, Yakovleva MA, Smitienko OA, Kolchugina IB, Round A, Gordeliy VI, Belushkin AV, and Ostrovsky MA
Subjects: Animals, Cattle, Cell Membrane chemistry, Membranes, Neutron Diffraction methods, Neutrons, Photoreceptor Cells metabolism, Photoreceptor Cells ultrastructure, Retina metabolism, Rhodopsin metabolism, Rhodopsin ultrastructure, Scattering, Small Angle, Photoreceptor Cells chemistry, Photoreceptor Cells physiology, Rhodopsin chemistry
Abstract: The supramolecular organization of the visual pigment rhodopsin in the photoreceptor membrane remains contentious. Specifically, whether this G protein-coupled receptor functions as a monomer or dimer remains unknown, as does the presence or absence of ordered packing of rhodopsin molecules in the photoreceptor membrane. Completely opposite opinions have been expressed on both issues. Herein, using small-angle neutron and X-ray scattering approaches, we performed a comparative analysis of the structural characteristics of the photoreceptor membrane samples in buffer, both in the outer segment of photoreceptor cells, and in the free photoreceptor disks. The average distance between the centers of two neighboring rhodopsin molecules was found to be ~5.8 nm in both cases. The results indicate an unusually high packing density of rhodopsin molecules in the photoreceptor membrane, but molecules appear to be randomly distributed in the membrane without any regular ordering., (Copyright © 2019 Elsevier B.V. All rights reserved.)
Published: 2019
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27. Structure and mechanisms of sodium-pumping KR2 rhodopsin.

Author: Kovalev K, Polovinkin V, Gushchin I, Alekseev A, Shevchenko V, Borshchevskiy V, Astashkin R, Balandin T, Bratanov D, Vaganova S, Popov A, Chupin V, Büldt G, Bamberg E, and Gordeliy V
Subjects: Bacterial Proteins chemistry, Bacterial Proteins metabolism, Hydrogen-Ion Concentration, Models, Molecular, Molecular Conformation, Mutation, Protein Binding, Protein Multimerization, Rhodopsin genetics, Rhodopsin metabolism, Sodium metabolism, Sodium-Potassium-Exchanging ATPase metabolism, Structure-Activity Relationship, Rhodopsin chemistry, Sodium chemistry, Sodium-Potassium-Exchanging ATPase chemistry
Abstract: Rhodopsins are the most universal biological light-energy transducers and abundant phototrophic mechanisms that evolved on Earth and have a remarkable diversity and potential for biotechnological applications. Recently, the first sodium-pumping rhodopsin KR2 from Krokinobacter eikastus was discovered and characterized. However, the existing structures of KR2 are contradictory, and the mechanism of Na + pumping is not yet understood. Here, we present a structure of the cationic (non H + ) light-driven pump at physiological pH in its pentameric form. We also present 13 atomic structures and functional data on the KR2 and its mutants, including potassium pumps, which show that oligomerization of the microbial rhodopsin is obligatory for its biological function. The studies reveal the structure of KR2 at nonphysiological low pH where it acts as a proton pump. The structure provides new insights into the mechanisms of microbial rhodopsins and opens the way to a rational design of novel cation pumps for optogenetics.
Published: 2019
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28. Small-angle X-ray scattering study of the kinetics of light-dark transition in a LOV protein.

Author: Röllen K, Granzin J, Batra-Safferling R, and Stadler AM
Subjects: Bacterial Proteins metabolism, Crystallography, X-Ray, Flavin Mononucleotide chemistry, Kinetics, Protein Domains, Protein Structure, Secondary, Spectrophotometry, Ultraviolet, X-Ray Diffraction, Flavoproteins metabolism, Oxygen metabolism, Photoreceptors, Microbial metabolism, Pseudomonas putida metabolism, Scattering, Small Angle
Abstract: Light, oxygen, voltage (LOV) photoreceptors consist of conserved photo-responsive domains in bacteria, archaea, plants and fungi, and detect blue-light via a flavin cofactor. We investigated the blue-light induced conformational transition of the dimeric photoreceptor PpSB1-LOV-R66I from Pseudomonas putida in solution by using small-angle X-ray scattering (SAXS). SAXS experiments of the fully populated light- and dark-states under steady-state conditions revealed significant structural differences between the two states that are in agreement with the known structures determined by crystallography. We followed the transition from the light- to the dark-state by using SAXS measurements in real-time. A two-state model based on the light- and dark-state conformations could describe the measured time-course SAXS data with a relaxation time τREC of ~ 34 to 35 min being larger than the recovery time found with UV/vis spectroscopy. Unlike the flavin chromophore-based UV/vis method that is sensitive to the local chromophore environment in flavoproteins, SAXS-based assay depends on protein conformational changes and provides with an alternative to measure the recovery kinetics., Competing Interests: The authors have declared that no competing interests exist. Authors affiliation to Forschungszentrum Jülich GmbH does not alter our adherence to PLOS ONE policies on sharing data and materials.
Published: 2018
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29. Efficient non-cytotoxic fluorescent staining of halophiles.

Author: Maslov I, Bogorodskiy A, Mishin A, Okhrimenko I, Gushchin I, Kalenov S, Dencher NA, Fahlke C, Büldt G, Gordeliy V, Gensch T, and Borshchevskiy V
Subjects: Fluorescent Dyes chemistry, Membrane Potentials, Microscopy, Fluorescence, Halobacteriaceae cytology, Halomonas cytology, Staining and Labeling methods
Abstract: Research on halophilic microorganisms is important due to their relation to fundamental questions of survival of living organisms in a hostile environment. Here we introduce a novel method to stain halophiles with MitoTracker fluorescent dyes in their growth medium. The method is based on membrane-potential sensitive dyes, which were originally used to label mitochondria in eukaryotic cells. We demonstrate that these fluorescent dyes provide high staining efficiency and are beneficial for multi-staining purposes due to the spectral range covered (from orange to deep red). In contrast with other fluorescent dyes used so far, MitoTracker does not affect growth rate, and remains in cells after several washing steps and several generations in cell culture. The suggested dyes were tested on three archaeal (Hbt. salinarum, Haloferax sp., Halorubrum sp.) and two bacterial (Salicola sp., Halomonas sp.) strains of halophilic microorganisms. The new staining approach provides new insights into biology of Hbt. salinarum. We demonstrated the interconversion of rod-shaped cells of Hbt. salinarium to spheroplasts and submicron-sized spheres, as well as the cytoplasmic integrity of giant rod Hbt. salinarum species. By expanding the variety of tools available for halophile detection, MitoTracker dyes overcome long-standing limitations in fluorescence microscopy studies of halophiles.
Published: 2018
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30. Inward H + pump xenorhodopsin: Mechanism and alternative optogenetic approach.

Author: Shevchenko V, Mager T, Kovalev K, Polovinkin V, Alekseev A, Juettner J, Chizhov I, Bamann C, Vavourakis C, Ghai R, Gushchin I, Borshchevskiy V, Rogachev A, Melnikov I, Popov A, Balandin T, Rodriguez-Valera F, Manstein DJ, Bueldt G, Bamberg E, and Gordeliy V
Subjects: Archaea metabolism, Binding Sites, Cell Line, Chromatography, High Pressure Liquid, Escherichia coli metabolism, Humans, Hydrogen-Ion Concentration, Light, Liposomes, Models, Molecular, Protein Binding, Protein Conformation, Protons, Retina metabolism, Rhodopsin chemistry, Spectrum Analysis, Optogenetics methods, Proton Pumps metabolism, Rhodopsin metabolism
Abstract: Generation of an electrochemical proton gradient is the first step of cell bioenergetics. In prokaryotes, the gradient is created by outward membrane protein proton pumps. Inward plasma membrane native proton pumps are yet unknown. We describe comprehensive functional studies of the representatives of the yet noncharacterized xenorhodopsins from Nanohaloarchaea family of microbial rhodopsins. They are inward proton pumps as we demonstrate in model membrane systems, Escherichia coli cells, human embryonic kidney cells, neuroblastoma cells, and rat hippocampal neuronal cells. We also solved the structure of a xenorhodopsin from the nanohalosarchaeon Nanosalina ( Ns XeR) and suggest a mechanism of inward proton pumping. We demonstrate that the Ns XeR is a powerful pump, which is able to elicit action potentials in rat hippocampal neuronal cells up to their maximal intrinsic firing frequency. Hence, inwardly directed proton pumps are suitable for light-induced remote control of neurons, and they are an alternative to the well-known cation-selective channelrhodopsins.
Published: 2017
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31. Effects of Coarse Graining and Saturation of Hydrocarbon Chains on Structure and Dynamics of Simulated Lipid Molecules.

Author: Buslaev P and Gushchin I
Abstract: Molecular dynamics simulations are used extensively to study the processes on biological membranes. The simulations can be conducted at different levels of resolution: all atom (AA), where all atomistic details are provided; united atom (UA), where hydrogen atoms are treated inseparably of corresponding heavy atoms; and coarse grained (CG), where atoms are grouped into larger particles. Here, we study the behavior of model bilayers consisting of saturated and unsaturated lipids DOPC, SOPC, OSPC and DSPC in simulations performed using all atom CHARMM36 and coarse grained Martini force fields. Using principal components analysis, we show that the structural and dynamical properties of the lipids are similar, both in AA and CG simulations, although the unsaturated molecules are more dynamic and favor more extended conformations. We find that CG simulations capture 75 to 100% of the major collective motions, overestimate short range ordering, result in more flexible molecules and 5-7 fold faster sampling. We expect that the results reported here will be useful for comprehensive quantitative comparisons of simulations conducted at different resolution levels and for further development and improvement of CG force fields.
Published: 2017
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32. Fast iodide-SAD phasing for high-throughput membrane protein structure determination.

Author: Melnikov I, Polovinkin V, Kovalev K, Gushchin I, Shevtsov M, Shevchenko V, Mishin A, Alekseev A, Rodriguez-Valera F, Borshchevskiy V, Cherezov V, Leonard GA, Gordeliy V, and Popov A
Subjects: Crystallography, X-Ray methods, Humans, Protein Domains, Iodides, Receptors, G-Protein-Coupled chemistry, Scattering, Small Angle
Abstract: We describe a fast, easy, and potentially universal method for the de novo solution of the crystal structures of membrane proteins via iodide-single-wavelength anomalous diffraction (I-SAD). The potential universality of the method is based on a common feature of membrane proteins-the availability at the hydrophobic-hydrophilic interface of positively charged amino acid residues with which iodide strongly interacts. We demonstrate the solution using I-SAD of four crystal structures representing different classes of membrane proteins, including a human G protein-coupled receptor (GPCR), and we show that I-SAD can be applied using data collection strategies based on either standard or serial x-ray crystallography techniques.
Published: 2017
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33. New Insights on Signal Propagation by Sensory Rhodopsin II/Transducer Complex.

Author: Ishchenko A, Round E, Borshchevskiy V, Grudinin S, Gushchin I, Klare JP, Remeeva A, Polovinkin V, Utrobin P, Balandin T, Engelhard M, Büldt G, and Gordeliy V
Subjects: Archaeal Proteins chemistry, Binding Sites, Halobacteriaceae metabolism, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Multimerization, Sensory Rhodopsins chemistry, Static Electricity, Structure-Activity Relationship, Archaeal Proteins metabolism, Sensory Rhodopsins metabolism, Signal Transduction
Abstract: The complex of two membrane proteins, sensory rhodopsin II (NpSRII) with its cognate transducer (NpHtrII), mediates negative phototaxis in halobacteria N. pharaonis. Upon light activation NpSRII triggers a signal transduction chain homologous to the two-component system in eubacterial chemotaxis. Here we report on crystal structures of the ground and active M-state of the complex in the space group I2 1 2 1 2 1 . We demonstrate that the relative orientation of symmetrical parts of the dimer is parallel ("U"-shaped) contrary to the gusset-like ("V"-shaped) form of the previously reported structures of the NpSRII/NpHtrII complex in the space group P2 1 2 1 2, although the structures of the monomers taken individually are nearly the same. Computer modeling of the HAMP domain in the obtained "V"- and "U"-shaped structures revealed that only the "U"-shaped conformation allows for tight interactions of the receptor with the HAMP domain. This is in line with existing data and supports biological relevance of the "U" shape in the ground state. We suggest that the "V"-shaped structure may correspond to the active state of the complex and transition from the "U" to the "V"-shape of the receptor-transducer complex can be involved in signal transduction from the receptor to the signaling domain of NpHtrII., Competing Interests: The authors declare no competing financial interests.
Published: 2017
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34. Structure of the light-driven sodium pump KR2 and its implications for optogenetics.

Author: Gushchin I, Shevchenko V, Polovinkin V, Borshchevskiy V, Buslaev P, Bamberg E, and Gordeliy V
Subjects: Binding Sites genetics, Crystallography, X-Ray, Ion Transport radiation effects, Light, Models, Chemical, Models, Molecular, Mutation, Photolysis radiation effects, Protein Engineering methods, Sodium chemistry, Sodium metabolism, Sodium-Potassium-Exchanging ATPase genetics, Sodium-Potassium-Exchanging ATPase metabolism, Protein Multimerization, Protein Structure, Secondary, Protein Structure, Tertiary, Sodium-Potassium-Exchanging ATPase chemistry
Abstract: A key and common process present in organisms from all domains of life is the maintenance of the ion gradient between the inside and the outside of the cell. The gradient is generated by various active transporters, among which are the light-driven ion pumps of the microbial rhodopsin family. Whereas the proton-pumping and anion-pumping rhodopsins have been known for a long time, the cation (sodium) pumps were described only recently. Following the discovery, high-resolution atomic structures of the pump KR2 were determined that revealed the complete ion translocation pathway, including the positions of the characteristic Asn-Asp-Gln (NDQ) triad, the unusual ion uptake cavity acting as a selectivity filter, the unique N-terminal α-helix, capping the ion release cavity, and unexpected flexibility of the retinal-binding pocket. The structures also revealed pentamerization of KR2 and binding of sodium ions at the interface. Finally, on the basis of the structures, potassium-pumping KR2 variants have been designed, making the findings even more important for optogenetic applications. In this Structural Snapshot, we analyse the implications of the structural findings for understanding the sodium translocation mechanism and application of the pump and its mutants in optogenetics., (© 2015 FEBS.)
Published: 2016
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35. Crystal structure of a light-driven sodium pump.

Author: Gushchin I, Shevchenko V, Polovinkin V, Kovalev K, Alekseev A, Round E, Borshchevskiy V, Balandin T, Popov A, Gensch T, Fahlke C, Bamann C, Willbold D, Büldt G, Bamberg E, and Gordeliy V
Subjects: Crystallography, X-Ray, Ion Transport, Models, Molecular, Potassium metabolism, Protein Structure, Tertiary, Sodium metabolism, Flavobacteriaceae enzymology, Rhodopsin ultrastructure, Sodium-Potassium-Exchanging ATPase ultrastructure
Abstract: Recently, the first known light-driven sodium pumps, from the microbial rhodopsin family, were discovered. We have solved the structure of one of them, Krokinobacter eikastus rhodopsin 2 (KR2), in the monomeric blue state and in two pentameric red states, at resolutions of 1.45 Å and 2.2 and 2.8 Å, respectively. The structures reveal the ion-translocation pathway and show that the sodium ion is bound outside the protein at the oligomerization interface, that the ion-release cavity is capped by a unique N-terminal α-helix and that the ion-uptake cavity is unexpectedly large and open to the surface. Obstruction of the cavity with the mutation G263F imparts KR2 with the ability to pump potassium. These results pave the way for the understanding and rational design of cation pumps with new specific properties valuable for optogenetics.
Published: 2015
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36. X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism.

Author: Nogly P, Gushchin I, Remeeva A, Esteves AM, Borges N, Ma P, Ishchenko A, Grudinin S, Round E, Moraes I, Borshchevskiy V, Santos H, Gordeliy V, and Archer M
Subjects: Amino Acid Sequence, Archaeal Proteins genetics, Archaeoglobus fulgidus chemistry, Archaeoglobus fulgidus genetics, Biocatalysis, Catalytic Domain, Cell Membrane chemistry, Cell Membrane genetics, Crystallography, X-Ray, Cytidine Diphosphate chemistry, Magnesium metabolism, Models, Molecular, Molecular Sequence Data, Phosphotransferases genetics, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Alignment, Archaeal Proteins chemistry, Archaeal Proteins metabolism, Archaeoglobus fulgidus enzymology, Cell Membrane enzymology, Cytidine Diphosphate metabolism, Phosphotransferases chemistry, Phosphotransferases metabolism
Abstract: Phospholipids have major roles in the structure and function of all cell membranes. Most integral membrane proteins from the large CDP-alcohol phosphatidyltransferase family are involved in phospholipid biosynthesis across the three domains of life. They share a conserved sequence pattern and catalyse the displacement of CMP from a CDP-alcohol by a second alcohol. Here we report the crystal structure of a bifunctional enzyme comprising a cytoplasmic nucleotidyltransferase domain (IPCT) fused with a membrane CDP-alcohol phosphotransferase domain (DIPPS) at 2.65 Å resolution. The bifunctional protein dimerizes through the DIPPS domains, each comprising six transmembrane α-helices. The active site cavity is hydrophilic and widely open to the cytoplasm with a magnesium ion surrounded by four highly conserved aspartate residues from helices TM2 and TM3. We show that magnesium is essential for the enzymatic activity and is involved in catalysis. Substrates docking is validated by mutagenesis studies, and a structure-based catalytic mechanism is proposed.
Published: 2014
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