Abstact

Microtubule nucleation by the gamma-tubulin ring complex (gammaTuRC) is spatiotemporally regulated and in higher eukaryotes is thought to involve a transition from an inactive open to an active closed conformation that matches the microtubule geometry. However, gammaTuRC activators only promote a partially closed conformation, raising the question of whether complete closure is required for activation. Combining in vitro nucleation assays and cryo-EM, we find that centrosomin motif 1 (CM1), a conserved element of several gammaTuRC regulators, potently accelerates human gammaTuRC-mediated microtubule nucleation by facilitating complete closure of gammaTuRC as the nascent microtubule assembles. A 3.7 A cryo-EM structure identifies the gammaTuRC latch and several interactions involved in conformational closure. Notably, the distinct subunits that keep gammaTuRC open and inactive in higher eukaryotes also participate in its closure and activation. This work provides additional insight into the logic of the human gammaTuRC architecture and its activation by CM1.