State-dependent sequential allostery exhibited by chaperonin TRiC/CCT revealed by network analysis of Cryo-EM maps
| Autor: | Jianhua Xing, José María Carazo, Yan Zhang, Ivet Bahar, Karolina Mikulska-Ruminska, James Krieger, Carlos Oscar S. Sorzano, Burak Tevfik Kaynak |
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| Přispěvatelé: | National Institutes of Health (US), Ministerio de Economía y Competitividad (España) |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Protein Conformation Cryo-electron microscopy Protein subunit 030303 biophysics Allosteric regulation Biophysics Heteromer Collective dynamics Topology representing network Supramolecular machines Chaperonin Structure-Activity Relationship 03 medical and health sciences Allosteric Regulation Molecular Biology ATP-mediated allosteric signalling 0303 health sciences Elastic network model Chemistry Cryoelectron Microscopy Folding (chemistry) Protein Subunits Cryo-EM electron density map Eukaryotic Cells State dependent sense organs Eukaryotic chaperonin TRiC/CCT Chaperonin Containing TCP-1 Network analysis |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0079-6107 |
| Popis: | The eukaryotic chaperonin TRiC/CCT plays a major role in assisting the folding of many proteins through an ATP-driven allosteric cycle. Recent structures elucidated by cryo-electron microscopy provide a broad view of the conformations visited at various stages of the chaperonin cycle, including a sequential activation of its subunits in response to nucleotide binding. But we lack a thorough mechanistic understanding of the structure-based dynamics and communication properties that underlie the TRiC/CCT machinery. In this study, we present a computational methodology based on elastic network models adapted to cryo-EM density maps to gain a deeper understanding of the structure-encoded allosteric dynamics of this hexadecameric machine. We have analysed several structures of the chaperonin resolved in different states toward mapping its conformational landscape. Our study indicates that the overall architecture intrinsically favours cooperative movements that comply with the structural variabilities observed in experiments. Furthermore, the individual subunits CCT1-CCT8 exhibit state-dependent sequential events at different states of the allosteric cycle. For example, in the ATP-bound state, subunits CCT5 and CCT4 selectively initiate the lid closure motions favoured by the overall architecture; whereas in the apo form of the heteromer, the subunit CCT7 exhibits the highest predisposition to structural change. The changes then propagate through parallel fluxes of allosteric signals to neighbours on both rings. The predicted state-dependent mechanisms of sequential activation provide new insights into TRiC/CCT intra- and inter-ring signal transduction events. Support is gratefully acknowledged from NIH grants P41 GM103712 and P30DA035778 (IB) and MINECO BIO2016-76400-R (JMC and COSS). |
| Databáze: | OpenAIRE |
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