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| Title | Cryo-EM structures of the tubulin cofactors reveal the molecular basis of alpha/beta-tubulin biogenesis. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2025 |
| Publish date | Dec 29, 2025 |
Authors | Aryan Taheri / Zhoaqian Wang / Bharti Singal / Fei Guo / Jawdat Al-Bassam / ![]() |
| 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, ...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. |
External links | Nat Commun / PubMed:41461644 |
| Methods | EM (single particle) |
| Resolution | 3.49 - 3.89 Å |
| Structure data | EMDB-47947, PDB-9edr: EMDB-47948, PDB-9eds: EMDB-47949, PDB-9edt: EMDB-47954, PDB-9eeb: ![]() EMDB-70497: Tubulin cofactors D, Arl2, tubulin dimer ![]() EMDB-70498: Tubulin cofactors D,E,G bound to tubulin dimer. Class 2 ![]() EMDB-70499: Tubulin cofactors D,E,G bound to tubulin dimer. Class 1 ![]() EMDB-70504: Tubulin Cofactors D,E,G,C and Tubulin complex -- TBCC N Terminus Bound to Tubulin Core Refinement ![]() EMDB-70505: Tubulin Cofactors D,E,G,C and Tubulin complex -- TBCC N Terminus Bound to Tubulin. TBCC Focused ![]() EMDB-70506: Tubulin Cofactors D,E,G,C and Tubulin complex -- TBCC N Terminus Bound to Tubulin. TBC E Refinement ![]() EMDB-70516: Tubulin cofactors D,E,G,C bound to tubulin dimer -- TBCC N terminus unbound. Core Refinement ![]() EMDB-70518: Tubulin cofactors D,E,G,C bound to tubulin dimer -- TBCC N terminus unbound. TBCE Refinement |
| Chemicals | ![]() ChemComp-GTP: ![]() ChemComp-GDP: |
| Source |
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Keywords | CYTOSOLIC PROTEIN / Cytoskeleton / tubulin / tubulin cofactors / microtubules / tubulin biogenesis / tubulin degredation / Cofactors / Tubulin biogeneis / Tubulin degradation |
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