The γ-tubulin ring complex (γ-TuRC) is an essential regulator of centrosomal and acentrosomal microtubule formation, yet its structure is not known. Here, we present a cryo-EM reconstruction of the native human γ-TuRC at ∼3.8 Å resolution, revealing an asymmetric, cone-shaped structure. Pseudo-atomic models indicate that GCP4, GCP5, and GCP6 form distinct Y-shaped assemblies that structurally mimic GCP2/GCP3 subcomplexes distal to the γ-TuRC "seam." We also identify an unanticipated structural bridge that includes an actin-like protein and spans the γ-TuRC lumen. Despite its asymmetric architecture, the γ-TuRC arranges γ-tubulins into a helical geometry poised to nucleate microtubules. Diversity in the γ-TuRC subunits introduces large (>100,000 Å2) surfaces in the complex that allow for interactions with different regulatory factors. The observed compositional complexity of the γ-TuRC could self-regulate its assembly into a cone-shaped structure to control microtubule formation across diverse contexts, e.g., within biological condensates or alongside existing filaments.

中文翻译：

---

人γ-管蛋白环复合物的不对称分子结构。

γ-微管蛋白环复合物（γ-TuRC）是中心体和中心体微管形成的重要调节剂，但其结构尚不清楚。在这里，我们提出了以约3.8Å分辨率对天然人γ-TuRC进行冷冻-EM重建的方法，揭示了一种不对称的锥形结构。伪原子模型表明，GCP4，GCP5和GCP6形成了不同的Y形组件，这些组件在结构上模仿了GCP2 / GCP3在γ-TuRC“接缝”远端的子复合体。我们还确定了一个意想不到的结构桥，其中包括肌动蛋白样蛋白，跨过γ-TuRC内腔。尽管具有非对称结构，但γ-TuRC仍将γ-微管蛋白排列成螺旋形，从而使微管成核。γ-TuRC亚基的多样性会在复合物中引入较大的表面（> 100,000Å2），从而可以与不同的调节因子相互作用。