Allosteric signaling of ATP hydrolysis in GroEL-GroES complexes.
The double-ring chaperonin GroEL and its lid-like cochaperonin GroES form asymmetric complexes that, in the ATP-bound state, mediate productive folding in a hydrophilic, GroES-encapsulated chamber, the so-called cis cavity. Upon ATP hydrolysis within the cis ring, the asymmetric complex becomes able to accept non-native polypeptides and ATP in the open, trans ring. Here we have examined the structural basis for this allosteric switch in activity by cryo-EM and single-particle image processing. ATP hydrolysis does not change the conformation of the cis ring, but its effects are transmitted through an inter-ring contact and cause domain rotations in the mobile trans ring. These rigid-body movements in the trans ring lead to disruption of its intra-ring contacts, expansion of the entire ring and opening of both the nucleotide pocket and the substrate-binding domains, admitting ATP and new substrate protein.
Ranson
Neil A
NA
Astbury Centre for Structural Molecular Biology and Institute of Molecular & Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Clare
Daniel K
DK
Farr
George W
GW
Houldershaw
David
D
Horwich
Arthur L
AL
Saibil
Helen R
HR
D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000494:Allosteric Regulation; D018835:Chaperonin 10 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018834:Chaperonin 60 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D006868:Hydrolysis; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary
D018835:Chaperonin 10; D018834:Chaperonin 60; D046912:Multiprotein Complexes; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate