A structural model for the autoinhibition of the γ-TuRC-activating CM1 domain

ABSTRACT: Microtubule nucleation by γ-tubulin ring complexes (γ-TuRCs) must be spatiotemporally controlled to avoid major cell division errors. γ-TuRCs are activated by the centrosome-specific binding of a highly conserved Centrosomin Motif 1 (CM1) domain, but how binding is prevented in the cytosol remains unclear. We provide the first structural explanation for CM1 autoinhibition, revealing that stable intramolecular interactions mediate cooperative folding to block γ-TuRC binding interfaces. Using various structural approaches, we show that the CM1 forms a conserved dimeric coiled-coil hairpin that sequesters a key phenylalanine residue essential for γ-TuRC binding. This appears sufficient for autoinhibition in humans, but in flies autoinhibition requires the additional association of an upstream “CM1 autoinhibition” (CAI) domain, which covers the opposite phenylalanine residue of the dimer. Collectively, the data provide the first structural model for CM1 autoinhibition and reveal evolutionary differences across species.

INSTRUMENT(S):

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

SUBMITTER: Sébastien Brier  

LAB HEAD: Sébastien Brier

PROVIDER: PXD077066 | Pride | 2026-10-01

REPOSITORIES: Pride