groel-groesreview98 - P1 rpk/vks P2 ARS 9:29 Annual Reviews...

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Annu. Rev. Biochem. 1998. 67:581–608 Copyright c 1998 by Annual Reviews. All rights reserved STRUCTURE AND FUNCTION IN GroEL-MEDIATED PROTEIN FOLDING Paul B. Sigler, 1,2 Zhaohui Xu, 1,2 Hays S. Rye, 2,3 Steven G. Burston, 3 Wayne A. Fenton, 3 and Arthur L. Horwich 2,3 1 Department of Molecular Biophysics and Biochemistry, 2 Howard Hughes Medical Institute, and 3 Department of Genetics, School of Medicine, Yale University, New Haven, Connecticut 06510; e-mail: [email protected] KEY WORDS: ATP, chaperonin, GroES, Hsp60 A BSTRACT Recent structural and biochemical investigations have come together to allow a better understanding of the mechanism of chaperonin (GroEL, Hsp60)–mediated protein folding, the final step in the accurate expression of genetic information. Major, asymmetric conformational changes in the GroEL double toroid accom- pany binding of ATP and the cochaperonin GroES. When a nonnative polypeptide, bound to one of the GroEL rings, is encapsulated by GroES to form a cis ternary complex, these changes drive the polypeptide into the sequestered cavity and initiate its folding. ATP hydrolysis in the cis ring primes release of the products, and ATP binding in the trans ring then disrupts the cis complex. This process allows the polypeptide to achieve its final native state, if folding was completed, or to recycle to another chaperonin molecule, if the folding process did not result in a form committed to the native state. CONTENTS PURPOSE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582 THE ROLE OF MOLECULAR CHAPERONES IN THE CELL . . . . . . . . . . . . . . . . . . . . . . . 582 Biological Catalysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582 The Entropic Barrier to Expressing Genes Accurately . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583 Categories of Molecular Chaperones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584 CHAPERONINS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585 Chaperonin Architecture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585 581 0066-4154/98/0701-0581$08.00 Annu. Rev. Biochem. 1998.67:581-608. Downloaded from arjournals.annualreviews.org by University of British Columbia Library on 11/03/09. For personal use only.
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582 SIGLER ET AL GroEL and GroES Structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 586 The Chaperonin Reaction Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 587 Phase I: Polypeptide Binding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 588 Phase II: Nucleotide and GroES Binding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592 The Asymmetrical GroEL-GroES-ADP Complex Structure . . . . . . . . . . . . . . . . . . . . . . . . 596 Phase III: Polypeptide Release and Folding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 600 Phase IV: Protein Folding and Release of Ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601 CONCLUSIONS AND PROSPECTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604 Certainty Versus Uncertainty in the Stereochemistry of the Folding Cycle . . . . . . . . . . . . 604 PURPOSE The main purpose of this review is to put forth an integrated structure/function analysis of chaperonin-assisted protein folding that coordinates recent high- resolution crystallographic results with functional studies in solution. To pro- vide an appropriate context, however, we first review where molecular chaper- ones fit in the scheme of biological catalysis and the special problems presented by the cell’s need for quick and accurate expression of genetic information, ul- timately in the form of properly folded functional proteins and their assemblies.
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