Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT.
All chaperonins mediate ATP-dependent polypeptide folding by confining substrates within a central chamber. Intriguingly, the eukaryotic chaperonin TRiC (also called CCT) uses a built-in lid to close the chamber, whereas prokaryotic chaperonins use a detachable lid. Here we determine the mechanism of lid closure in TRiC using single-particle cryo-EM and comparative protein modeling. Comparison of TRiC in its open, nucleotide-free, and closed, nucleotide-induced states reveals that the interdomain motions leading to lid closure in TRiC are radically different from those of prokaryotic chaperonins, despite their overall structural similarity. We propose that domain movements in TRiC are coordinated through unique interdomain contacts within each subunit and, further, these contacts are absent in prokaryotic chaperonins. Our findings show how different mechanical switches can evolve from a common structural framework through modification of allosteric networks.
Graduate Program in Structural and Computational Biology and Molecular Biophysics, One Baylor Plaza, Baylor College of Medicine, Houston, Texas 77030, USA.
Christopher R
CR
Booth
Anne S
AS
Meyer
Yao
Y
Cong
Maya
M
Topf
Andrej
A
Sali
Steven J
SJ
Ludtke
Wah
W
Chiu
Judith
J
Frydman
D000818:Animals; D002417:Cattle; D018834:Chaperonin 60 / Q000737:chemistry / Q000378:metabolism; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
D018834:Chaperonin 60; D021122:Protein Subunits; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins