Partial closure of the γ-tubulin ring complex by CDK5RAP2 activates microtubule nucleation
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Date
2024-12-02
Publication Type
Journal Article
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yes
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Abstract
Microtubule nucleation is templated by the γ-tubulin ring complex (γ-TuRC), but its structure deviates from the geometry of α-/β-tubulin in the microtubule, explaining the complex’s poor nucleating activity. Several proteins may activate the γ-TuRC, but the mechanisms underlying activation are not known. Here, we determined the structure of the porcine γ-TuRC purified using CDK5RAP2’s centrosomin motif 1 (CM1). We identified an unexpected conformation of the γ-TuRC bound to multiple protein modules containing MZT2, GCP2, and CDK5RAP2, resulting in a long-range constriction of the γ-tubulin ring that brings it in closer agreement with the 13-protofilament microtubule. Additional CDK5RAP2 promoted γ-TuRC decoration and stimulated the microtubule-nucleating activities of the porcine γ-TuRC and a reconstituted, CM1-free human complex in single-molecule assays. Our results provide a structural mechanism for the control of microtubule nucleation by CM1 proteins and identify conformational transitions in the γ-TuRC that prime it for microtubule nucleation.
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published
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Journal / series
Volume
59 (23)
Pages / Article No.
3161 - 3174000000000000000
Publisher
Cell Press
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Date created
Subject
Organisational unit
09763 - Wieczorek, Michal / Wieczorek, Michal
02030 - Dep. Biologie / Dep. of Biology
Notes
Funding
208120 - The Regulation of Microtubule Architecture by the gamma-Tubulin Ring Complex (SNF)
211309 - Dynamic Molecular Model of the Microtubule Plus End (SNF)
211309 - Dynamic Molecular Model of the Microtubule Plus End (SNF)