Metal bridges between the PhoQ sensor domain and the membrane regulate transmembrane signaling
Metal bridges between the PhoQ sensor domain and the membrane regulate transmembrane signaling
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DOI：
10.1016/j.jmb.2005.12.032
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发表时间：
2006-03-10
影响因子：
5.6
通讯作者：
Xu, WQ
中科院分区：
文献类型：
--
作者：
Cho, US;Bader, MW;Xu, WQ
细菌组氨酸激酶通过将信号从胞质外传感器结构域转导到胞质催化结构域来响应环境刺激。其中，PhoQ促进细菌毒力，并被二价阳离子如钙和镁紧密抑制。我们已经确定了PhoQ传感器结构域从鼠伤寒沙门氏菌在Ca 2+结合状态，这揭示了一个高度带负电荷的表面，是在靠近内膜的晶体结构。这种酸性表面结合至少三种Ca 2+，介导PhoQ-膜相互作用。突变分析表明，在膜近端区域的PhoQ传感器域的结构完整性，促进金属介导的抑制。我们提出，耗尽或二价阳离子的位移导致电荷之间的排斥PhoQ和膜，这启动跨膜信号通过改变方向之间的PhoQ传感器域和膜。因此，PhoQ和膜都是胞外传感和跨膜信号传导所必需的。出版社：Elsevier Ltd
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. Published by Elsevier Ltd.