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PMID: 18311152 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

GroEL stimulates protein folding through forced unfolding.

Nature structural & molecular biology ·Vol. 15 ·No. 3 ·2008-03-00 ·Pages 303-11

Lin Z, Madan D, Rye HS

Abstract

Many proteins cannot fold without the assistance of chaperonin machines like GroEL and GroES. The nature of this assistance, however, remains poorly understood. Here we demonstrate that unfolding of a substrate protein by GroEL enhances protein folding. We first show that capture of a protein on the open ring of a GroEL-ADP-GroES complex, GroEL's physiological acceptor state for non-native proteins in vivo, leaves the substrate protein in an unexpectedly compact state. Subsequent binding of ATP to the same GroEL ring causes rapid, forced unfolding of the substrate protein. Notably, the fraction of the substrate protein that commits to the native state following GroES binding and protein release into the GroEL-GroES cavity is proportional to the extent of substrate-protein unfolding. Forced protein unfolding is thus a central component of the multilayered stimulatory mechanism used by GroEL to drive protein folding.

MeSH Terms
Adenosine Diphosphate/metabolism Adenosine Triphosphate/metabolism Apoproteins/metabolism Chaperonin 60/chemistry,metabolism Cysteine Models, Biological Peptide Hydrolases/metabolism Protein Binding Protein Conformation Protein Folding Ribulose-Bisphosphate Carboxylase/chemistry
Chemicals
Apoproteins Chaperonin 60 Adenosine Diphosphate Adenosine Triphosphate Peptide Hydrolases Ribulose-Bisphosphate Carboxylase Cysteine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lin Zong
Department of Molecular Biology, Princeton University, Schultz Laboratory, Princeton, New Jersey 08544, USA.
Madan Damian
Rye Hays S
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1394
Published
2008-03-00
Epub
2008-00-02
Pages
303-11
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3744391
Subset
IM
Grants
NIGMS NIH HHS · R01 GM065421 · United States
NIGMS NIH HHS · GM065421 · United States
External Links
PubMed source DOI: 10.1038/nsmb.1394 PMC Full Text View journal details
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