EMD-51010
Structure of the Position 10 to 12 Open gamma-Tubulin Ring Complex from Pig Brain
EMD-51010
Single-particle4.9 Å
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Map released: 09/10/2024
Last modified: 18/12/2024
Sample Organism:
Sus scrofa
Sample: Gamma-Tubulin Ring Complex in native pig brain
Deposition Authors: Munoz-Hernandez H
,
Wieczorek M
Sample: Gamma-Tubulin Ring Complex in native pig brain
Deposition Authors: Munoz-Hernandez H
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Partial closure of the gamma-tubulin ring complex by CDK5RAP2 activates microtubule nucleation.
Xu Y,
Munoz-Hernandez H
,
Krutyholowa R,
Marxer F,
Cetin F,
Wieczorek M
(2024) Dev Cell , 59 , 3161 - 3174.e15
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(2024) Dev Cell , 59 , 3161 - 3174.e15
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.
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.