EMD-32989

Single-particle
4.2 Å
EMD-32989 Deposition: 01/03/2022
Map released: 07/06/2023
Last modified: 05/07/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-32989

Cryo-EM structure of human TRiC-tubulin-S2

EMD-32989

Single-particle
4.2 Å
EMD-32989 Deposition: 01/03/2022
Map released: 07/06/2023
Last modified: 05/07/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Human TRiC-tubulin-S2
Fitted models: 7x3j (Avg. Q-score: 0.246)

Deposition Authors: Cong Y , Liu CX
Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM.
Liu C , Jin M, Wang S, Han W, Zhao Q, Wang Y , Xu C, Diao L , Yin Y , Peng C , Bao L , Wang Y , Cong Y
(2023) Commun Biol , 6 , 531 - 531
PUBMED: 37193829
DOI: doi:10.1038/s42003-023-04915-x
ISSN: 2399-3642
Abstract:
The eukaryotic chaperonin TRiC/CCT assists the folding of about 10% of cytosolic proteins through an ATP-driven conformational cycle, and the essential cytoskeleton protein tubulin is the obligate substrate of TRiC. Here, we present an ensemble of cryo-EM structures of endogenous human TRiC throughout its ATPase cycle, with three of them revealing endogenously engaged tubulin in different folding stages. The open-state TRiC-tubulin-S1 and -S2 maps show extra density corresponding to tubulin in the cis-ring chamber of TRiC. Our structural and XL-MS analyses suggest a gradual upward translocation and stabilization of tubulin within the TRiC chamber accompanying TRiC ring closure. In the closed TRiC-tubulin-S3 map, we capture a near-natively folded tubulin-with the tubulin engaging through its N and C domains mainly with the A and I domains of the CCT3/6/8 subunits through electrostatic and hydrophilic interactions. Moreover, we also show the potential role of TRiC C-terminal tails in substrate stabilization and folding. Our study delineates the pathway and molecular mechanism of TRiC-mediated folding of tubulin along the ATPase cycle of TRiC, and may also inform the design of therapeutic agents targeting TRiC-tubulin interactions.