Department of Chemistry, Louisiana State University, Baton Range, LA, 70803, USA.
National Magnetic Resonance Facility at Madison and Biochemistry Department, University of Wisconsin- Madison, Madison, WI, 53706, USA.
Biomol NMR Assign. 2020 Oct;14(2):301-307. doi: 10.1007/s12104-020-09965-4. Epub 2020 Jul 2.
Chlamydia trachomatis is an obligate intracellular bacterium that causes the most common sexually transmitted bacterial diseases in the world. With a biphasic developmental cycle, the bacteria utilize a type III secretion system (T3SS) to invade host cells as infectious elemental bodies, which then differentiate into actively dividing reticulate bodies. The regulation of the developmental cycle and the T3SS are linked by the bi-functional protein, specific Chlamydia chaperone 4 (Scc4). Scc4 is a class I T3SS chaperone forming a heterodimer with specific Chlamydia chaperone 1 (Scc1) to chaperone the essential virulence effector, Chlamydia outer membrane protein N. Scc4 also functions as a transcription factor by binding to the RNA polymerase holoenzyme between the flap region of the β subunit and region 4 of σ. In order to investigate the mechanism behind Scc4's dual functions and target its protein-protein interactions as a route for drug development, the structure and dynamics of Scc4 are being pursued. In the course of this effort, we assigned 89.2% of the backbone and sidechain H, N, and C resonances of full-length Scc4. The assigned chemical shifts were used to predict the secondary structure and dynamic properties. The type and order of Scc4's determined secondary structure are consistent with the X-ray crystal structures of other bacterial T3SS chaperones.
沙眼衣原体是一种专性细胞内细菌，可引起世界上最常见的性传播细菌病。该细菌具有两相发育周期，利用 III 型分泌系统（T3SS）将感染元素体侵入宿主细胞，然后分化为活跃分裂的网状体。发育周期和 T3SS 的调节通过双功能蛋白，特异性沙眼衣原体伴侣 4（Scc4）连接。Scc4 是一种 I 类 T3SS 伴侣蛋白，与特异性沙眼衣原体伴侣 1（Scc1）形成异二聚体，伴侣必需的毒力效应因子，沙眼衣原体外膜蛋白 N。Scc4 还作为转录因子，通过结合 RNA 聚合酶全酶的β亚基的瓣状区和σ4 区起作用。为了研究 Scc4 双重功能背后的机制，并将其蛋白-蛋白相互作用作为药物开发的途径，正在研究 Scc4 的结构和动力学。在这一努力过程中，我们对全长 Scc4 的 89.2%的骨架和侧链 H、N 和 C 共振进行了归属。归属的化学位移用于预测二级结构和动态特性。Scc4 确定的二级结构的类型和顺序与其他细菌 T3SS 伴侣的 X 射线晶体结构一致。
