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Abstract：
The Helicobacter pylori Cag type IV secretion system (Cag T4SS) has an important role in the pathogenesis of gastric cancer. The Cag T4SS outer membrane core complex (OMCC) is organized into three regions: a 14-fold symmetric outer membrane cap (OMC) composed of CagY, CagX, CagT, CagM, and Cag3; a 17-fold symmetric periplasmic ring (PR) composed of CagY and CagX; and a stalk with unknown composition. We investigated how CagT, CagM, and a conserved antenna projection (AP) region of CagY contribute to the structural organization of the OMCC. Single-particle cryo-EM analyses showed that complexes purified from ΔcagT or ΔcagM mutants no longer had organized OMCs, but the PRs remained structured. OMCCs purified from a CagY antenna projection mutant (CagY∆AP) were structurally similar to WT OMCCs, except for the absence of the α-helical antenna projection. These results indicate that CagY and CagX are sufficient for maintaining a stable PR, but the organization of the OMC requires CagY, CagX, CagM, and CagT. Our results highlight an unexpected structural independence of two major subdomains of the Cag T4SS OMCC.
摘要：
幽门螺杆菌CagⅣ型分泌系统(CagT4SS)在胃癌的发病机制中具有重要作用。CagT4SS外膜核心复合物（OMCC）分为三个区域：由CagY组成的14倍对称外膜帽（OMC），CagX,CagT,CagM,和Cag3；由CagY和CagX组成的17倍对称周质环（PR）；和组成未知的茎。我们调查了CagT,CagM,CagY的保守天线投影（AP）区域有助于OMCC的结构组织。单颗粒低温EM分析表明，从ΔcagT或ΔcagM突变体中纯化的复合物不再具有组织化的OMC，但PR保持结构化。从CagY天线投射突变体(CagYΔAP)纯化的OMCC在结构上与WTOMCC相似，除了没有α螺旋天线投影。这些结果表明，CagY和CagX足以保持稳定的PR，但是OMC的组织需要CagY，CagX,CagM,还有CagT.我们的结果突出了CagT4SSOMCC的两个主要子域的意外结构独立性。
