Identification of an internal cavity in the PhoQ sensor domain for PhoQ activity and SafA-mediated control
Identification of an internal cavity in the PhoQ sensor domain for PhoQ activity and SafA-mediated control
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DOI：
10.1080/09168451.2018.1562879
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发表时间：
2019-04
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影响因子：
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通讯作者：
K. Yoshitani;E. Ishii;K. Taniguchi;H. Sugimoto;Y. Shiro;Y. Akiyama;加藤 明宣;R. Utsumi;Y. Eguchi
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文献类型：
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作者：
K. Yoshitani;E. Ishii;K. Taniguchi;H. Sugimoto;Y. Shiro;Y. Akiyama;加藤 明宣;R. Utsumi;Y. Eguchi
摘要 PhoQ/PhoP 双组分信号转导系统在多种革兰氏阴性菌中保守，常参与病原体毒力的表达。小内膜蛋白 SafA 独立于控制 PhoQ 活性的其他已知信号激活大肠杆菌中的 PhoQ。我们之前已经证明，SafA 直接与 PhoQ 周质区域的传感器结构域 (PhoQ-SD) 相互作用进行激活，并且 PhoQ-SD 中的 D179R 突变会减弱 SafA 对 PhoQ 的激活。在本研究中，野生型 PhoQ-SD 和 D179R 的结构比较揭示了该结构域中央核心中发现的空腔（SD（感觉结构域）口袋）的差异。这是两种蛋白质之间唯一的结构差异。 SD 口袋周围残基的定点诱变支持 SD 口袋作为参与 PhoQ 活性的位点。此外，SD 口袋也被证明参与 SafA 介导的 PhoQ 控制。图解摘要 SD 口袋周围的残基影响 SafA 介导的 PhoQ 激活
ABSTRACT The PhoQ/PhoP two-component signal transduction system is conserved in various Gram-negative bacteria and is often involved in the expression of virulence in pathogens. The small inner membrane protein SafA activates PhoQ in Escherichia coli independently from other known signals that control PhoQ activity. We have previously shown that SafA directly interacts with the sensor domain of the periplasmic region of PhoQ (PhoQ-SD) for activation, and that a D179R mutation in PhoQ-SD attenuates PhoQ activation by SafA. In this study, structural comparison of wild-type PhoQ-SD and D179R revealed a difference in the cavity (SD (sensory domain) pocket) found in the central core of this domain. This was the only structural difference between the two proteins. Site-directed mutagenesis of the residues surrounding the SD pocket has supported the SD pocket as a site involved in PhoQ activity. Furthermore, the SD pocket has also been shown to be involved in SafA-mediated PhoQ control. Graphical Abstract Residues surrounding the SD pocket that affect SafA-mediated PhoQ activation