Microtubules are composed of α-tubulin and β-tubulin dimers positioned head-to-tail to form protofilaments that associate laterally in varying numbers. It is not known how cellular microtubules assemble with the canonical 13-protofilament architecture, resulting in micrometer-scale α/β-tubulin tracks for intracellular transport that align with, rather than spiral along, the long axis of the filament. We report that the human ~2.3 MDa γ-tubulin ring complex (γ-TuRC), an essential regulator of microtubule formation that contains 14 γ-tubulins, selectively nucleates 13-protofilament microtubules. Cryogenic electron microscopy reconstructions of γ-TuRC-capped microtubule minus ends reveal the extensive intra-domain and inter-domain motions of γ-TuRC subunits that accommodate luminal bridge components and establish lateral and longitudinal interactions between γ-tubulins and α-tubulins. Our structures suggest that γ-TuRC, an inefficient nucleation template owing to its splayed conformation, can transform into a compacted cap at the microtubule minus end and set the lattice architecture of cellular microtubules.

微管由头尾相连的 α-微管蛋白和 β-微管蛋白二聚体组成，形成以不同数量横向连接的原丝。目前尚不清楚细胞微管如何与规范的 13 原丝结构组装，从而产生微米级的 α/β-微管蛋白轨道，用于细胞内运输，与丝的长轴对齐，而不是沿着丝的长轴螺旋。我们报道了人类 ~2.3 MDa γ-微管蛋白环复合物 (γ-TuRC)，它是微管形成的重要调节因子，含有 14 个 γ-微管蛋白，选择性地使 13 个原丝微管成核。 γ-TuRC 加帽微管负端的低温电子显微镜重建揭示了 γ-TuRC 亚基广泛的域内和域间运动，这些运动容纳管腔桥组件并建立 γ-微管蛋白和 α-微管蛋白之间的横向和纵向相互作用。我们的结构表明，γ-TuRC（由于其张开构象而成为一种低效成核模板）可以在微管负端转化为致密帽，并设定细胞微管的晶格结构。