7TTN

The beta-tubulin folding intermediate II

Summary for 7TTN

• Entry DOI: 10.2210/pdb7ttn/pdb
• Related: 7TRG 7TTT 7TUB
• EMDB information: 26120
• Descriptor: Tubulin beta chain, ALUMINUM FLUORIDE, MAGNESIUM ION, ... (13 entities in total)
• Functional Keywords: human chaperonin tric with beta-tubulin folding intermediate ii, chaperone
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 528650.22

Authors

Zhao, Y.,Frydman, J.,Chiu, W. (deposition date: 2022-02-01, release date: 2022-12-28, Last modification date: 2024-06-12)

Primary citation

Gestaut, D.,Zhao, Y.,Park, J.,Ma, B.,Leitner, A.,Collier, M.,Pintilie, G.,Roh, S.H.,Chiu, W.,Frydman, J.
Structural visualization of the tubulin folding pathway directed by human chaperonin TRiC/CCT.
Cell, 185:4770-4787.e20, 2022

PubMed Abstract: The ATP-dependent ring-shaped chaperonin TRiC/CCT is essential for cellular proteostasis. To uncover why some eukaryotic proteins can only fold with TRiC assistance, we reconstituted the folding of β-tubulin using human prefoldin and TRiC. We find unstructured β-tubulin is delivered by prefoldin to the open TRiC chamber followed by ATP-dependent chamber closure. Cryo-EM resolves four near-atomic-resolution structures containing progressively folded β-tubulin intermediates within the closed TRiC chamber, culminating in native tubulin. This substrate folding pathway appears closely guided by site-specific interactions with conserved regions in the TRiC chamber. Initial electrostatic interactions between the TRiC interior wall and both the folded tubulin N domain and its C-terminal E-hook tail establish the native substrate topology, thus enabling C-domain folding. Intrinsically disordered CCT C termini within the chamber promote subsequent folding of tubulin's core and middle domains and GTP-binding. Thus, TRiC's chamber provides chemical and topological directives that shape the folding landscape of its obligate substrates.

PubMed: 36493755
DOI: 10.1016/j.cell.2022.11.014

Experimental method

ELECTRON MICROSCOPY (3.3 Å)