9EDR

Tubulin Cofactors D,E,G,C and Tubulin complex -- TBCC N Terminus Bound to Tubulin

Summary for 9EDR

• Entry DOI: 10.2210/pdb9edr/pdb
• EMDB information: 47947
• Descriptor: Chromosome instability protein 1, GTP-binding protein CIN4, Tubulin alpha-1A chain, ... (9 entities in total)
• Functional Keywords: cytoskeleton, tubulin, tubulin cofactors, microtubules, tubulin biogenesis, tubulin degredation, cytosolic protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 7
• Total formula weight: 329639.78

Authors

Taheri, A.,Al-bassam, J. (deposition date: 2024-11-17, release date: 2026-02-04)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.8 Å)