Nature子刊：奥地利科学家首次实现病菌毒素注入宿主细胞过程可

奥地利科学院的研究人员首次实现病菌毒素分子注入宿主细胞的过程可视化。相关文章发表于2013年12月8日的《Nature Structural & molecular Biology》杂志上。

3型分泌系统(T3SS)是一类高度保守的蛋白机制，通过将细菌毒素分子(又名毒力因子)直接注入宿主细胞从而控制宿主细胞的功能。T3SS的核心是一种稳定存在细菌内的类似于注射器的针状复合物，研究人员确信这种复合物为毒力因子进入目标细胞提供了途径。

Thomas Marlovits等人利用结构生物学和成像技术展示了沙门氏菌T3SS是如何将毒力因子转移到宿主细胞内的。他们利用一种经改良的底物分子建立了注射器的3D模型并将底物分泌过程中的整个T3SS装置可视化。Marlovits等人发现底物分子穿过了注射复合物中间的“孔”，这表明毒力因子为了进入宿主细胞一定会先展开。

由于T3SS对各种病菌的毒性至关重要，因此阻断病菌通过T3SS进入宿主细胞的途径或可成为抵抗细菌感染的一种潜在治疗手段。

原文摘要：

Structure of a pathogenic type 3 secretion system in action

Julia RADIcs, Lisa Königsmaier & Thomas C Marlovits

Type 3 secretion systems use 3.5-megadalton syringe-like, membrane-embedded 'injectisomes', each containing an ~800-Å-long needle complex to connect intracellular compartments of infectious bacteria and hosts. Here we identify requirements for substrate association with, transport through and exit from the injectisome of Salmonella enterica serovar Typhimurium. This guided the design of substrates that become trapped within the secretion path and enabled visualization of injectisomes in action in situ. We used cryo-EM to define the secretion path, providing a structural explanation as to why effector proteins must be unfolded during transport. Furthermore, trapping of a heterologous substrate in the needle prevents secretion of natural bacterial effectors. Together, the data reveal the path of protein secretion across multiple membranes and show that mechanisms rejecting unacceptable substrates can be undermined, and transport of bacterial effectors across an already assembled type 3 secretion system can be inhibited.

;