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The Dynamic Conformational Cycle of the Group I Chaperonin C-Termini Revealed via Molecular Dynamics Simulation

Journal Article · · PLoS ONE
 [1];  [2];  [2]
  1. Stanford University, CA (United States); Stanford Univ., CA (United States)
  2. Stanford University, CA (United States)
+ Show Author Affiliations
Chaperonins are large ring shaped oligomers that facilitate protein folding by encapsulation within a central cavity. All chaperonins possess flexible C-termini which protrude from the equatorial domain of each subunit into the central cavity. Biochemical evidence suggests that the termini play an important role in the allosteric regulation of the ATPase cycle, in substrate folding and in complex assembly and stability. Despite the tremendous wealth of structural data available for numerous orthologous chaperonins, little structural information is available regarding the residues within the C-terminus. Herein, molecular dynamics simulations are presented which localize the termini throughout the nucleotide cycle of the group I chaperonin, GroE, from Escherichia coli. The simulation results predict that the termini undergo a heretofore unappreciated conformational cycle which is coupled to the nucleotide state of the enzyme. As such, these results have profound implications for the mechanism by which GroE utilizes nucleotide and folds client proteins.
Research Organization:
Stanford University, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0008504
OSTI ID:
1904758
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 3 Vol. 10; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (3)

GroEL actively stimulates folding of the endogenous substrate protein PepQ journal June 2017
Formation of tRNA wobble inosine in humans is perturbed by a millennia-old mutation linked to intellectual disability journal March 2018
Formation of tRNA Wobble Inosine in Humans Is Disrupted by a Millennia-Old Mutation Causing Intellectual Disability journal October 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
adenosine triphosphatase
biochemical simulations
biophysical simulations
crystal structure
molecular dynamics
monomers
nucleotides
protein folding