title: The chaperonin ATPase cycle: mechanism of allosteric switching and movements of substrate-binding domains in GroEL.
abstract: Chaperonin-assisted protein folding proceeds through cycles of ATP binding and hydrolysis by the large chaperonin GroEL, which undergoes major allosteric rearrangements. Interaction between the two back-to-back seven-membered rings of GroEL plays an important role in regulating binding and release of folding substrates and of the small chaperonin GroES. Using cryo-electron microscopy, we have obtained three-dimensional reconstructions to 30 A resolution for GroEL and GroEL-GroES complexes in the presence of ADP, ATP, and the nonhydrolyzable ATP analog, AMP-PNP. Nucleotide binding to the equatorial domains of GroEL causes large rotations of the apical domains, containing the GroES and substrate protein-binding sites. We propose a mechanism for allosteric switching and describe conformational changes that may be involved in critical steps of folding for substrates encapsulated by GroES.
authors.affiliation: Department of Crystallography, Birkbeck College, University of London, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Roseman
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: White
authors.forename: K
authors.initials: K
authors.lastname: Braig
authors.forename: H R
authors.initials: HR
authors.lastname: Saibil
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000502:physiology; D001665:Binding Sites; D018835:Chaperonin 10 / Q000502:physiology; D018834:Chaperonin 60 / Q000502:physiology*; D004926:Escherichia coli; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008958:Models, Molecular; D009068:Movement; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D018835:Chaperonin 10; D018834:Chaperonin 60; D046911:Macromolecular Substances; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases