Structural basis of human γTuRC closure during CM1-activated microtubule nucleation

Microtubule nucleation by the γ-tubulin ring complex (γTuRC) 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, γTuRC 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 γTuRC regulators, potently accelerates human γTuRC-mediated microtubule nucleation by facilitating complete closure of γTuRC as the nascent microtubule assembles. A 3.7 Å cryo-EM structure identifies the γTuRC latch and several interactions involved in conformational closure. Notably, the distinct subunits that keep γTuRC open and inactive in higher eukaryotes also participate in its closure and activation. This work provides additional insight into the logic of the human γTuRC architecture and its activation by CM1. Here the authors show that CM1 activates human γTuRC by facilitating its complete closure as the nascent microtubule assembles: high-resolution cryo-EM identifies interactions that promote and stabilise the activated conformation.