The mechanism of GroEL/GroES folding/refolding of protein substrates revisited
The mechanism of GroEL/GroES folding/refolding of protein substrates revisited
Engineering Village 2
2006 Elsevier Inc
Accession number: 06149798113
Title: The mechanism of GroEL/GroES folding/refolding of protein substrates revisited
Authors: Jones, Huw; Preuss, Monika; Wright, Michael; Miller, Andrew D.
Author affiliation: Department of Chemistry Imperial College London, Imperial College Genetic Therapies Centre, Imperial College London, London, SW7 2AZ, United Kingdom
Serial title: Organic and Biomolecular Chemistry
Abbreviated serial title: Org. Biomol. Chem.
Volume: v 4
Issue: n 7
Publication year: 2006
Pages: p 1223-1235
Language: English
ISSN: 1477-0520
Document type: Journal article (JA)
Publisher: Royal Society of Chemistry, Cambridge, CB4 OWF, United Kingdom
Abstract: The thermodynamics and kinetics of zinc-cytochrome c (ZnCyt c) interactions with Escherichia coli molecular chaperone GroEL (Chaperonin 60; Cpn60) are described. Zinc(ii)-porphyrhin represents a flexible fluorescent probe for thermodynamic complex formation between GroEL and ZnCyt c, as well as for stopped-flow fluorescence kinetic experiments. Data suggests that GroEL and GroEL/GroES-assisted refolding of unfolded ZnCyt c takes place by a mechanism that is quite close to the Anfinsen Cage hypothesis for molecular chaperone activity. However, even in the presence of ATP, GroEL/GroES-assisted refolding of ZnCyt c takes place at approximately half the rate of refolding of ZnCyt c alone. On the other hand, there is little evidence for refolding behaviour consistent with the Iterative Annealing hypothesis. This includes a complete lack of GroEL or GroEL/GroES-assisted enhancement of refolding rate constant k2 associated with the unfolding of a putative misfolded state IHNC (Zn) on the pathway to the native state. Reviewing our data in the light of data from other laboratories, we observe that all forward rate enhancements or reductions could be accounted for in terms of thermodynamic coupling (adjusting positions of refolding equilibria) due to binding interactions between GroEL and unfolded protein substrates, driven by thermodynamic considerations. Therefore, we propose that passive kinetic partitioning should be considered the core mechanism of the GroEL/GroES molecular chaperone machinery, wherein the core function is to bind unfolded protein substrates leading to a blockade of aggregation pathways and to increases in molecular flux through productive folding pathway(s). ? The Royal Society of Chemistry 2006.
Number of references: 55
Ei main heading: Proteins
Ei controlled terms: Cytology - Reaction kinetics - Escherichia coli - Complexation - Thermodynamic properties - Fluorescence
Uncontrolled terms: GroEL/GroES - Folding/refolding - Molecular chaperones - Thermodynamic couplings
Ei classification codes: 804.1 Organic Compounds - 461.2 Biological Materials - 802.2 Chemical Reactions - 461.9 Biology - 641.1 Thermodynamics - 741.1 Light/Optics
Treatment: Literature review (LIT); Theoretical (THR); Experimental (EXP)
DOI: 10.1039/b517879g
Database: Compendex
Compilation and indexing terms, ? 2006 Elsevier Inc. All rights reserved
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