小柯机器人

近日，美国洛克菲勒大学Tarun M. Kapoor及其研究团队解析了人类γ-微管蛋白环复合物（γ-TuRC）的不对称分子结构。这一研究成果2019年12月17日在线发表在国际学术期刊《细胞》上。

研究人员报道了约3.8Å分辨率的天然人类γ-TuRC冷冻电镜结构重建，从而揭示了一种不对称的锥形结构。伪原子模型表明，GCP4、GCP5和GCP6形成截然不同的Y形组件，其在结构上模拟了γ-TuRC“缝”远端的GCP2/GCP3亚复合物。研究人员还发现了一个意外的结构桥，其中包括肌动蛋白样蛋并跨越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，以使微管聚集。γ-TuRC亚基的多样性会在复合物中引入较大的表面（大于 100,000Ų），从而可以与不同的调节因子相互作用。观察到的γ-TuRC组成复杂性可以自我调节其组装成锥形结构，从而在各种情况下（例如在生物浓缩物中或与现有长丝并排）控制微管的形成。

据了解，γ-TuRC是中心体和中心体微管形成的重要调节者，但其结构尚不清楚。

附：英文原文

Title: Asymmetric Molecular Architecture of the Human γ-Tubulin Ring Complex

Author: Michal Wieczorek, Linas Urnavicius, Shih-Chieh Ti, Kelly R. Molloy, Brian T. Chait, Tarun M. Kapoor

Issue&Volume: December 17, 2019

Abstract: The γ-tubulin ring complex (γ-TuRC) is an essential regulator of centrosomal and acentrosomalmicrotubule formation, yet its structure is not known. Here, we present a cryo-EMreconstruction of the native human γ-TuRC at ～3.8 resolution, revealing an asymmetric,cone-shaped structure. Pseudo-atomic models indicate that GCP4, GCP5, and GCP6 formdistinct Y-shaped assemblies that structurally mimic GCP2/GCP3 subcomplexes distalto the γ-TuRC “seam.” We also identify an unanticipated structural bridge that includesan 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 2) surfaces in the complex that allow for interactions with different regulatory factors.The observed compositional complexity of the γ-TuRC could self-regulate its assemblyinto a cone-shaped structure to control microtubule formation across diverse contexts,e.g., within biological condensates or alongside existing filaments.

DOI: 10.1016/j.cell.2019.12.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31369-8