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| Title | Structural dissection of αβ-tubulin heterodimer assembly and disassembly by human tubulin-specific chaperones. |
|---|---|
| Journal, issue, pages | Science, Vol. 390, Issue 6772, Page eady2708, Year 2025 |
| Publish date | Oct 30, 2025 |
Authors | Yeonjae Seong / Hyunmin Kim / Kyumi Byun / Yeon-Woo Park / Soung-Hun Roh / ![]() |
| 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 ...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. |
External links | Science / PubMed:41166473 |
| Methods | EM (single particle) |
| Resolution | 2.14 - 3.59 Å |
| Structure data | ![]() EMDB-63376: Consensus map of the TBC-DE-Arl2-beta-tubulin complex with GTP ![]() EMDB-63377: Local refinement map of Arl2 in the TBC-DE-Arl2-beta-tubulin-GTP complex ![]() EMDB-63378: Local refinement map of AR3 domain in the TBC-DE-Arl2-beta-tubulin-GTP complex ![]() EMDB-63546: Consensus map of the TBC-DE-Arl2-alpha-beta-tubulin complex with GTP ![]() EMDB-63547: Local refinement map of TBCE and alpha-tubulin in the TBC-DE-Arl2-alpha-beta-tubulin-GTP complex ![]() EMDB-63548: Local refinement map of Arl2 and TBCD-AR1 domain in the TBC-DE-Arl2-alpha-beta-tubulin-GTP complex ![]() EMDB-63549: Consensus map of the TBC-DEC-Arl2-alpha-beta-tubulin complex with GDP-AlFx ![]() EMDB-63550: Local refinement map of TBCE in the TBC-DEC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63551: Local refinement map of TBCE and alpha-tubulin in the TBC-DEC-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63552: Local refinement map of TBCC-RPD and Arl2 in the TBC-DEC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63553: Local refinement map of TBCD and Arl2 in the TBC-DEC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63554: Consensus map of the TBC-DC-Arl2-alpha-beta-tubulin complex with GDP-AlFx ![]() EMDB-63555: Local refinement map of alpha-tubulin in the TBC-DC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63556: Local refinement map of TBCD and Arl2 in the TBC-DC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63557: Local refinement map of TBCC-RPD and Arl2 in the TBC-DC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63558: Local refinement map of TBCD AR3 domain in the TBC-DC-Arl2-alpha-beta-tubulin-GDP-AlFx complex ![]() EMDB-63569: Consensus map of the TBC-DE-Arl2-beta-tubulin complex ![]() EMDB-63570: Local refinement map of TBCE-LRRD in the TBC-DE-Arl2-beta-tubulin complex EMDB-63572, PDB-9m1i: EMDB-63573, PDB-9m1j: EMDB-63574, PDB-9m1k: EMDB-63575, PDB-9m1l: EMDB-63576, PDB-9m1m: EMDB-63577, PDB-9m1n: |
| Chemicals | ![]() ChemComp-GTP: ![]() ChemComp-MG: ![]() ChemComp-GDP: ![]() ChemComp-AF3: |
| Source |
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Keywords | CHAPERONE / complex |
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