7TRG

The beta-tubulin folding intermediate I

7TRG の概要

• エントリーDOI: 10.2210/pdb7trg/pdb
• EMDBエントリー: 26089
• 分子名称: Tubulin beta chain, MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (13 entities in total)
• 機能のキーワード: human chaperonin tric with beta-tubulin folding intermediate i, chaperone
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 528669.27

構造登録者

Zhao, Y.,Frydman, J.,Chiu, W. (登録日: 2022-01-28, 公開日: 2022-12-28, 最終更新日: 2024-06-12)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3 Å)