Visualizing nucleation, condensation and propagation of β-tubulin folding in chaperonin TRiC

Zhao, Yanyan; Schmid, Michael F.; Chiu, Wah

doi:10.1101/2024.10.13.618036

Visualizing nucleation, condensation and propagation of β-tubulin folding in chaperonin TRiC

Journal Article · Tue Aug 12 00:00:00 EDT 2025 · BioRxiv

DOI:https://doi.org/10.1101/2024.10.13.618036· OSTI ID:2575658

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AbstractThe folding nucleus (FN) initiates protein folding and enables an efficient folding pathway. Here we directly visualize the tubulin FN consisting of a nonnative, partially assembled Rossmann fold, in the closed chamber of human chaperonin TRiC. Chaperonin TRiC interacts with non-natively folded secondary structural elements, stabilizing the nucleus for transition into its first native domain. Through progressive folding, the unfolded sequence goes through drastic spatial arrangement in the TRiC chamber to sample the conformational space, mediated by the highly dynamic CCT tails. The observed presence of individual nonnative secondary structures first in the nonnative FN and then around the incrementally folded native domains supports the hypothesis that tubulin folding in TRiC is a hierarchical process of nucleation, condensation and propagation in cooperation with TRiC subunits.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 2575658

Journal Information:: BioRxiv, Journal Name: BioRxiv

Publisher:: Cold Spring Harbor LaboratoryCopyright Statement

Country of Publication:: United States

Language:: English

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