7X0A

Cryo-EM structure of human TRiC-NPP state

Summary for 7X0A

• Entry DOI: 10.2210/pdb7x0a/pdb
• EMDB information: 32922
• Descriptor: T-complex protein 1 subunit alpha, T-complex protein 1 subunit beta, T-complex protein 1 subunit delta, ... (8 entities in total)
• Functional Keywords: tubulin, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 16
• Total formula weight: 946716.47

Authors

Cong, Y.,Liu, C.X. (deposition date: 2022-02-21, release date: 2023-04-12, Last modification date: 2024-06-26)

Primary citation

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.
Pathway and mechanism of tubulin folding mediated by TRiC/CCT along its ATPase cycle revealed using cryo-EM.
Commun Biol, 6:531-531, 2023

PubMed 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.

PubMed: 37193829
DOI: 10.1038/s42003-023-04915-x

Experimental method

ELECTRON MICROSCOPY (3.1 Å)