7X3J
Cryo-EM structure of human TRiC-tubulin-S2
Summary for 7X3J
Entry DOI | 10.2210/pdb7x3j/pdb |
EMDB information | 32989 |
Descriptor | T-complex protein 1 subunit alpha, T-complex protein 1 subunit beta, T-complex protein 1 subunit delta, ... (9 entities in total) |
Functional Keywords | structural protein |
Biological source | Homo sapiens (human) More |
Total number of polymer chains | 16 |
Total formula weight | 954831.37 |
Authors | |
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 Cited by 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: 37193829DOI: 10.1038/s42003-023-04915-x PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
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