PDF(Pubmed)
Abstract：
Chemotaxis is a fundamental process whereby bacteria seek out nutrient sources and avoid harmful chemicals. For the symbiotic soil bacterium Sinorhizobium meliloti, the chemotaxis system also plays an essential role in the interaction with its legume host. The chemotactic signaling cascade is initiated through interactions of an attractant or repellent compound with chemoreceptors or methyl-accepting chemotaxis proteins (MCPs). S. meliloti possesses eight chemoreceptors to mediate chemotaxis. Six of these receptors are transmembrane proteins with periplasmic ligand-binding domains (LBDs). The specific functions of McpW and McpZ are still unknown. Here, we report the crystal structure of the periplasmic domain of McpZ (McpZPD) at 2.7 Å resolution. McpZPD assumes a novel fold consisting of three concatenated four-helix bundle modules. Through phylogenetic analyses, we discovered that this helical tri-modular domain fold arose within the Rhizobiaceae family and is still evolving rapidly. The structure, offering a rare view of a ligand-free dimeric MCP-LBD, reveals a novel dimerization interface. Molecular dynamics calculations suggest ligand binding will induce conformational changes that result in large horizontal helix movements within the membrane-proximal domains of the McpZPD dimer that are accompanied by a 5 Å vertical shift of the terminal helix toward the inner cell membrane. These results suggest a mechanism of transmembrane signaling for this family of MCPs that entails both piston-type and scissoring movements. The predicted movements terminate in a conformation that closely mirrors those observed in related ligand-bound MCP-LBDs.
摘要：
趋化性是细菌寻找营养来源并避免有害化学物质的基本过程。对于共生土壤细菌中华根瘤菌，趋化系统在与豆类宿主的相互作用中也起着至关重要的作用。趋化信号级联是通过引诱剂或驱避剂化合物与化学感受器或甲基接受趋化蛋白(MCP)的相互作用引发的。S.meliloti具有八种化学感受器来介导趋化性。这些受体中的六种是具有周质配体结合结构域(LBD)的跨膜蛋白。McpW和McpZ的具体功能仍然未知。这里,我们以2.7µ分辨率报告了McpZ（McpZPD）的周质结构域的晶体结构。McpZPD假定由三个串联的四螺旋束模块组成的新型折叠。通过系统发育分析，我们发现这种螺旋三模块结构域折叠出现在根瘤菌科内，并且仍在迅速发展。结构,提供了一种罕见的无配体二聚体MCP-LBD，揭示了一种新颖的二聚化界面。分子动力学计算表明，配体结合将诱导构象变化，从而导致McpZPD二聚体的膜近端结构域内的大的水平螺旋运动，并伴随着末端螺旋向内部细胞膜的垂直移动。这些结果表明，该MCP家族的跨膜信号传导机制需要活塞式和剪断式运动。预测的运动终止于紧密反映在相关配体结合的MCP-LBD中观察到的构象。
