Structural investigation of a chaperonin in action reveals how nucleotide binding regulates the functional cycle
| Autor: | Guillaume Mas, Pierre Gans, Paul Schanda, Elisa Colas Debled, Guy Schoehn, Pavel Macek, Christine Moriscot, Jérôme Boisbouvier, Jia-Ying Guan, Elodie Crublet |
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| Přispěvatelé: | 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), 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) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Conformation Archaeal Proteins media_common.quotation_subject Group II Chaperonins Protein aggregation 010402 general chemistry 01 natural sciences Chaperonin 03 medical and health sciences Adenosine Triphosphate Nucleotide Internalization Nuclear Magnetic Resonance Biomolecular Protein Unfolding media_common chemistry.chemical_classification Multidisciplinary biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Chemistry Malate Synthase Chaperonin 60 biology.organism_classification 0104 chemical sciences Adenosine Diphosphate Folding (chemistry) 030104 developmental biology Biophysics Muramidase HSP60 Protein folding Pyrococcus horikoshii Archaea |
| Zdroj: | Science Advances Science Advances, American Association for the Advancement of Science (AAAS), 2018, 4 (9), pp.eaau4196. ⟨10.1126/sciadv.aau4196⟩ Science Advances, 2018, 4 (9), pp.eaau4196. ⟨10.1126/sciadv.aau4196⟩ |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aau4196⟩ |
| Popis: | International audience; Chaperonins are ubiquitous protein assemblies present in bacteria, eukaryota, and archaea, facilitating the folding of proteins, preventing protein aggregation, and thus participating in maintaining protein homeostasis in the cell. During their functional cycle, they bind unfolded client proteins inside their double ring structure and promote protein folding by closing the ring chamber in an adenosine 5'-triphosphate (ATP)-dependent manner. Although the static structures of fully open and closed forms of chaperonins were solved by x-ray crystallography or electron microscopy, elucidating the mechanisms of such ATP-driven molecular events requires studying the proteins at the structural level under working conditions. We introduce an approach that combines site-specific nuclear magnetic resonance observation of very large proteins, enabled by advanced isotope labeling methods, with an in situ ATP regeneration system. Using this method, we provide functional insight into the 1-MDa large hsp60 chaperonin while processing client proteins and reveal how nucleotide binding, hydrolysis, and release control switching between closed and open states. While the open conformation stabilizes the unfolded state of client proteins, the internalization of the client protein inside the chaperonin cavity speeds up its functional cycle. This approach opens new perspectives to study structures and mechanisms of various ATP-driven biological machineries in the heat of action. |
| Databáze: | OpenAIRE |
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