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GroEL/GroES: structure and function of a two-stroke folding machine.
J Struct Biol. 1998 Dec 15; 124(2-3):129-41.JS

Abstract

Recent structural and functional studies have greatly advanced our understanding of the mechanism by which chaperonins (Cpn60) mediate protein folding, the final step in the accurate expression of genetic information. Escherichia coli GroEL has a symmetric double-toroid architecture, which binds nonnative polypeptide substrates on the hydrophobic walls of its central cavity. The asymmetric binding of ATP and cochaperonin GroES to GroEL triggers a major conformational change in the cis ring, creating an enlarged chamber into which the bound nonnative polypeptide is released. The structural changes that create the cis assembly also change the lining of the cavity wall from hydrophobic to hydrophilic, conducive to folding into the native state. ATP hydrolysis in the cis ring weakens it and primes the release of products. When ATP and GroES bind to the trans ring, it forms a stronger assembly, which disassembles the cis complex through negative cooperativity between rings. The opposing function of the two rings operates as if the system had two cylinders, one expelling the products of the reaction as the other loads up the reactants. One cycle of the reaction gives the polypeptide about 15 s to fold at the cost of seven ATP molecules. For some proteins, several cycles of GroEL assistance may be needed in order to achieve their native states.

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Authors+Show Affiliations

Xu Z
Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue, New Haven, Connecticut, 06520-8114, USA.
Sigler PB
No affiliation info available

MeSH

Adenosine TriphosphateBinding SitesChaperonin 10Chaperonin 60Escherichia coliModels, MolecularProtein ConformationProtein FoldingProtein Structure, Secondary

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

10049801

Citation

Xu, Z, and P B. Sigler. "GroEL/GroES: Structure and Function of a Two-stroke Folding Machine." Journal of Structural Biology, vol. 124, no. 2-3, 1998, pp. 129-41.
Xu Z, Sigler PB. GroEL/GroES: structure and function of a two-stroke folding machine. J Struct Biol. 1998;124(2-3):129-41.
Xu, Z., & Sigler, P. B. (1998). GroEL/GroES: structure and function of a two-stroke folding machine. Journal of Structural Biology, 124(2-3), 129-41.
Xu Z, Sigler PB. GroEL/GroES: Structure and Function of a Two-stroke Folding Machine. J Struct Biol. 1998 Dec 15;124(2-3):129-41. PubMed PMID: 10049801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GroEL/GroES: structure and function of a two-stroke folding machine. AU - Xu,Z, AU - Sigler,P B, PY - 1999/3/2/pubmed PY - 1999/3/2/medline PY - 1999/3/2/entrez SP - 129 EP - 41 JF - Journal of structural biology JO - J Struct Biol VL - 124 IS - 2-3 N2 - Recent structural and functional studies have greatly advanced our understanding of the mechanism by which chaperonins (Cpn60) mediate protein folding, the final step in the accurate expression of genetic information. Escherichia coli GroEL has a symmetric double-toroid architecture, which binds nonnative polypeptide substrates on the hydrophobic walls of its central cavity. The asymmetric binding of ATP and cochaperonin GroES to GroEL triggers a major conformational change in the cis ring, creating an enlarged chamber into which the bound nonnative polypeptide is released. The structural changes that create the cis assembly also change the lining of the cavity wall from hydrophobic to hydrophilic, conducive to folding into the native state. ATP hydrolysis in the cis ring weakens it and primes the release of products. When ATP and GroES bind to the trans ring, it forms a stronger assembly, which disassembles the cis complex through negative cooperativity between rings. The opposing function of the two rings operates as if the system had two cylinders, one expelling the products of the reaction as the other loads up the reactants. One cycle of the reaction gives the polypeptide about 15 s to fold at the cost of seven ATP molecules. For some proteins, several cycles of GroEL assistance may be needed in order to achieve their native states. SN - 1047-8477 UR - https://www.unboundmedicine.com/medline/citation/10049801/GroEL/GroES:_structure_and_function_of_a_two_stroke_folding_machine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1047-8477(98)94060-6 DB - PRIME DP - Unbound Medicine ER -