9EDT

Tubulin cofactors D,E,G bound to tubulin dimer

9EDT の概要

• エントリーDOI: 10.2210/pdb9edt/pdb
• EMDBエントリー: 47949
• 分子名称: Chromosome instability protein 1, GTP-binding protein CIN4, Tubulin alpha-1A chain, ... (8 entities in total)
• 機能のキーワード: tubulin, cofactors, tubulin cofactors, tubulin biogenesis, tubulin degradation, microtubules, cytosolic protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 301095.45

構造登録者

Taheri, A.,Al-bassam, J. (登録日: 2024-11-18, 公開日: 2026-02-04)

主引用文献

Taheri, A.,Wang, Z.,Singal, B.,Guo, F.,Al-Bassam, J.
Cryo-EM structures of the tubulin cofactors reveal the molecular basis of alpha/beta-tubulin biogenesis.
Nat Commun, 2025

PubMed Abstract: Microtubule polarity and dynamic polymerization arise from the self-association properties of the αβ-tubulin heterodimer. For decades, it has remained unclear how the tubulin cofactors TBCD, TBCE, TBCC, and the Arl2 GTPase mediate the biogenesis of αβ-tubulin from individual α- and β-tubulins. Here, we use cryo-electron microscopy to determine structures of tubulin cofactors bound to αβ-tubulin. TBCD, TBCE, and Arl2 form a heterotrimeric cage-like assembly, we term TBC-DEG, around the αβ-tubulin heterodimer. The TBC-DEG-αβ-tubulin structures show that TBC-DEG wraps around β-tubulin while TBCE extends along α-tubulin. The TBC-DEG/TBCC-αβ-tubulin structures reveal that TBCC forms multi-domain interactions with Arl2 and TBCD to engage the αβ-tubulin intradimer-interface, promoting TBCE rotation while TBCD holds β-tubulin. TBCC engages the GTP-bound Arl2, multiple sites of TBCD, and the native αβ-tubulin intradimer interface near the α-tubulin N-site GTP. Together, these structures uncover transition states for αβ-tubulin biogenesis and degradation, suggesting a vise-like, GTP-hydrolysis-dependent mechanism in which TBCC binding to TBC-DEG modulates αβ-tubulin interfaces. Our studies provide structural evidence that tubulin cofactors act as enzymatic regulators that assemble the invariant αβ-tubulin architecture. By catalyzing α- and β-tubulin biogenesis and degradation, the TBC-DEG and TBCC assemblies regulate the polymerization competency of αβ-tubulin for microtubule formation.

PubMed: 41461644
DOI: 10.1038/s41467-025-68142-0

実験手法

ELECTRON MICROSCOPY (3.7 Å)