9M1L

Cryo-EM structure of the TBC-DE-Arl2-alpha-beta-tubulin complex with GTP

9M1L の概要

• エントリーDOI: 10.2210/pdb9m1l/pdb
• EMDBエントリー: 63575
• 分子名称: Tubulin-specific chaperone D, ADP-ribosylation factor-like protein 2, Tubulin-specific chaperone E, ... (7 entities in total)
• 機能のキーワード: chaperone, complex
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 314643.06

構造登録者

Seong, Y.J.,Kim, H.M.,Byun, K.M.,Park, Y.W.,Roh, S.H. (登録日: 2025-02-26, 公開日: 2025-10-22, 最終更新日: 2025-11-12)

主引用文献

Seong, Y.,Kim, H.,Byun, K.,Park, Y.W.,Roh, S.H.
Structural dissection of alpha beta-tubulin heterodimer assembly and disassembly by human tubulin-specific chaperones.
Science, 390:eady2708-eady2708, 2025

PubMed Abstract: Microtubule assembly requires a set of chaperones known as tubulin-binding cofactors (TBCs). We used cryo-electron microscopy to visualize how human TBCD, TBCE, TBCC, and guanosine triphosphatase (GTPase) Arl2 mediate αβ-tubulin assembly and disassembly. We captured multiple conformational states, revealing how TBCs orchestrate tubulin heterodimer biogenesis. TBCD stabilizes monomeric β-tubulin and scaffolds the other cofactors. Guanosine triphosphate (GTP) binding to Arl2 induces conformational changes that toggle the complex between assembly and disassembly. TBCD and TBCE guide α- and β-tubulin into a partially assembled interface, and TBCC, acting as a molecular clamp, completes the heterodimer. TBCD also functions as a GTPase activating protein for β-tubulin. β-tubulin GTP hydrolysis is coupled to Arl2's GTPase activity, establishing a checkpoint that ensures that only fully matured heterodimers proceed. These findings provide a structural framework for tubulin heterodimer biogenesis and recycling, supporting cytoskeletal proteostasis.

PubMed: 41166473
DOI: 10.1126/science.ady2708

実験手法

ELECTRON MICROSCOPY (2.55 Å)