Cho Uhn Soo, Bader Martin W, Amaya Maria F, Daley Margaret E, Klevit Rachel E, Miller Samuel I, Xu Wenqing
Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
J Mol Biol. 2006 Mar 10;356(5):1193-206. doi: 10.1016/j.jmb.2005.12.032. Epub 2005 Dec 27.
Bacterial histidine kinases respond to environmental stimuli by transducing a signal from an extracytosolic sensor domain to a cytosolic catalytic domain. Among them, PhoQ promotes bacterial virulence and is tightly repressed by the divalent cations such as calcium and magnesium. We have determined the crystal structure of the PhoQ sensor domain from Salmonella typhimurium in the Ca2+-bound state, which reveals a highly negatively charged surface that is in close proximity to the inner membrane. This acidic surface binds at least three Ca2+, which mediate the PhoQ-membrane interaction. Mutagenesis analysis indicates that structural integrity at the membrane proximal region of the PhoQ sensor domain promotes metal-mediated repression. We propose that depletion or displacement of divalent cations leads to charge repulsion between PhoQ and the membrane, which initiates transmembrane signaling through a change in orientation between the PhoQ sensor domain and membrane. Therefore, both PhoQ and the membrane are required for extracytosolic sensing and transmembrane signaling.
细菌组氨酸激酶通过将信号从胞外传感器结构域传递到胞质催化结构域来响应环境刺激。其中，PhoQ促进细菌毒力，并受到钙和镁等二价阳离子的严格抑制。我们已经确定了鼠伤寒沙门氏菌PhoQ传感器结构域在结合Ca2+状态下的晶体结构，该结构揭示了一个高度带负电荷的表面，该表面靠近内膜。这个酸性表面结合至少三个Ca2+，它们介导PhoQ与膜的相互作用。诱变分析表明，PhoQ传感器结构域膜近端区域的结构完整性促进金属介导的抑制作用。我们提出，二价阳离子的耗尽或置换会导致PhoQ与膜之间的电荷排斥，从而通过PhoQ传感器结构域与膜之间方向的改变启动跨膜信号传导。因此，PhoQ和膜对于胞外传感和跨膜信号传导都是必需的。
