为了进入上皮细胞,专性细胞内病原体肺炎衣原体分泌早期效应蛋白,它们结合并调节宿主细胞的质膜,并募集几种关键的内吞宿主蛋白。这里,我们提出了进入相关的衣原体效应蛋白的高分辨率结构,SemD.SemD与其宿主结合伴侣的共结晶表明SemD共选择Cdc42结合位点以激活肌动蛋白细胞骨架调节剂N-WASP,使活跃,GTP结合的Cdc42是多余的。虽然SemD与N-WASP的结合比Cdc42强得多,它不结合Cdc42效应蛋白FMNL2,表明效应蛋白特异性。此外,通过识别灵活和结构化的领域,我们表明SemD可以同时与膜相互作用,内吞蛋白SNX9和N-WASP。这里,我们在结构水平上展示了单个效应蛋白如何劫持宿主内吞系统的中心成分以实现有效的内化。
To enter epithelial cells, the obligate intracellular pathogen Chlamydia pneumoniae secretes early effector proteins, which bind to and modulate the host-cell\'s plasma membrane and recruit several pivotal endocytic host proteins. Here, we present the high-resolution structure of an entry-related chlamydial effector protein, SemD. Co-crystallisation of SemD with its host binding partners demonstrates that SemD co-opts the Cdc42 binding site to activate the actin cytoskeleton regulator N-WASP, making active, GTP-bound Cdc42 superfluous. While SemD binds N-WASP much more strongly than Cdc42 does, it does not bind the Cdc42 effector protein FMNL2, indicating effector protein specificity. Furthermore, by identifying flexible and structured domains, we show that SemD can simultaneously interact with the membrane, the endocytic protein SNX9, and N-WASP. Here, we show at the structural level how a single effector protein can hijack central components of the host\'s endocytic system for efficient internalization.