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Titleγ-TuRC asymmetry induces local protofilament mismatch at the RanGTP-stimulated microtubule minus end.
Journal, issue, pagesEMBO J, Year 2024
Publish dateApr 10, 2024
AuthorsBram Ja Vermeulen / Anna Böhler / Qi Gao / Annett Neuner / Erik Župa / Zhenzhen Chu / Martin Würtz / Ursula Jäkle / Oliver J Gruss / Stefan Pfeffer / Elmar Schiebel /
PubMed AbstractThe γ-tubulin ring complex (γ-TuRC) is a structural template for de novo microtubule assembly from α/β-tubulin units. The isolated vertebrate γ-TuRC assumes an asymmetric, open structure ...The γ-tubulin ring complex (γ-TuRC) is a structural template for de novo microtubule assembly from α/β-tubulin units. The isolated vertebrate γ-TuRC assumes an asymmetric, open structure deviating from microtubule geometry, suggesting that γ-TuRC closure may underlie regulation of microtubule nucleation. Here, we isolate native γ-TuRC-capped microtubules from Xenopus laevis egg extract nucleated through the RanGTP-induced pathway for spindle assembly and determine their cryo-EM structure. Intriguingly, the microtubule minus end-bound γ-TuRC is only partially closed and consequently, the emanating microtubule is locally misaligned with the γ-TuRC and asymmetric. In the partially closed conformation of the γ-TuRC, the actin-containing lumenal bridge is locally destabilised, suggesting lumenal bridge modulation in microtubule nucleation. The microtubule-binding protein CAMSAP2 specifically binds the minus end of γ-TuRC-capped microtubules, indicating that the asymmetric minus end structure may underlie recruitment of microtubule-modulating factors for γ-TuRC release. Collectively, we reveal a surprisingly asymmetric microtubule minus end protofilament organisation diverging from the regular microtubule structure, with direct implications for the kinetics and regulation of nucleation and subsequent modulation of microtubules during spindle assembly.
External linksEMBO J / PubMed:38600243
MethodsEM (single particle)
Resolution17.0 Å
Structure data

EMDB-19861, PDB-9eoj:
Vertebrate microtubule-capping gamma-tubulin ring complex
Method: EM (single particle) / Resolution: 17.0 Å

Source
  • xenopus laevis (African clawed frog)
KeywordsCELL CYCLE / cytoskeleton / microtubule / microtubule nucleation / complex / template / cap / gamma-tubulin / gamma-tubulin ring complex

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