Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536.
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536
Proc Natl Acad Sci U S A. 2021 Nov 2;118(44). doi: 10.1073/pnas.2114552118.
Type III secretion systems are multiprotein molecular machines required for the virulence of several important bacterial pathogens. The central element of these machines is the injectisome, a ∼5-Md multiprotein structure that mediates the delivery of bacterially encoded proteins into eukaryotic target cells. The injectisome is composed of a cytoplasmic sorting platform, and a membrane-embedded needle complex, which is made up of a multiring base and a needle-like filament that extends several nanometers from the bacterial surface. The needle filament is capped at its distal end by another substructure known as the tip complex, which is crucial for the translocation of effector proteins through the eukaryotic cell plasma membrane. Here we report the cryo-EM structure of the Typhimurium needle tip complex docked onto the needle filament tip. Combined with a detailed analysis of structurally guided mutants, this study provides major insight into the assembly and function of this essential component of the type III secretion protein injection machine.
III 型分泌系统是多种蛋白分子机器，是几种重要的细菌病原体毒力所必需的。这些机器的核心元件是注射器，这是一个约 5MD 的多蛋白结构，介导细菌编码的蛋白递送至真核靶细胞。注射器由细胞质分选平台和膜嵌入的针状复合物组成，针状复合物由多环底座和从细菌表面延伸数纳米的针状细丝组成。针状细丝的远端由另一个称为尖端复合物的亚结构帽封住，这对于效应蛋白穿过真核细胞质膜的易位至关重要。在这里，我们报告了与针状细丝尖端对接的 Typhimurium 针尖端复合物的冷冻电镜结构。结合对结构导向突变体的详细分析，这项研究为 III 型分泌蛋白注射机器的这个基本组件的组装和功能提供了主要的见解。
