A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases.
A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases.
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pH 门控构象开关调节双功能 HisKA 家族组氨酸激酶的磷酸酶活性
DOI：
10.1038/s41467-017-02310-9
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发表时间：
2017-12-13
影响因子：
16.6
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Liu Y;Rose J;Huang S;Hu Y;Wu Q;Wang D;Li C;Liu M;Zhou P;Jiang L
组氨酸激酶是细菌双组分系统中的关键调节因子，介导细胞对环境变化的反应。绝大多数传感器组氨酸激酶属于双功能 HisKA 家族，对其底物表现出激酶和磷酸酶活性。调节这些酶的相反活性的分子机制尚不清楚。通过对来自海栖热袍菌的组氨酸激酶 HK853 及其反应调节剂 RR468 进行核磁共振和晶体学联合研究，我们在此报告了 HK853 的 pH 介导的构象转换，该转换在酸性条件下关闭其磷酸酶活性。这种 pH 传感机制在肠沙门氏菌的 EnvZ-OmpR 双组分系统中得到了体外和体内的进一步证明，这直接影响了细菌的感染性。我们的发现揭示了一种广泛保守的机制，该机制可响应环境 pH 的变化来调节双功能组氨酸激酶最大家族的磷酸酶活性。细菌通过二元系统（TCS）介导的信号转导来适应不断变化的环境条件。在这里，作者结合 X 射线晶体学和 NMR 研究来表征 pH 门控构象开关，该开关调节 TCS 双功能组氨酸激酶的磷酸酶活性。
Histidine kinases are key regulators in the bacterial two-component systems that mediate the cellular response to environmental changes. The vast majority of the sensor histidine kinases belong to the bifunctional HisKA family, displaying both kinase and phosphatase activities toward their substrates. The molecular mechanisms regulating the opposing activities of these enzymes are not well understood. Through a combined NMR and crystallographic study on the histidine kinase HK853 and its response regulator RR468 from Thermotoga maritima, here we report a pH-mediated conformational switch of HK853 that shuts off its phosphatase activity under acidic conditions. Such a pH-sensing mechanism is further demonstrated in the EnvZ-OmpR two-component system from Salmonella enterica in vitro and in vivo, which directly contributes to the bacterial infectivity. Our finding reveals a broadly conserved mechanism that regulates the phosphatase activity of the largest family of bifunctional histidine kinases in response to the change of environmental pH. Bacteria adapt to changing environmental conditions through signal transduction mediated by the two-component system (TCS). Here, the authors combine X-ray crystallography and NMR studies to characterize a pH-gated conformational switch that regulates the phosphatase activity of TCS bifunctional histidine kinases.
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影响因子：
15
作者：
Anderson, Kurtis M.;Esadze, Alexandre;Manoharan, Mariappan;Brueschweiler, Rafael;Gorenstein, David G.;Iwahara, Junji
通讯作者：
Iwahara, Junji
影响因子：
5.7
作者：
Podgornaia, Anna I.;Casino, Patricia;Marina, Alberto;Laub, Michael T.
通讯作者：
Laub, Michael T.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1016/j.bbapap.2007.02.005
发表时间：
2007-05-01
影响因子：
3.2
作者：
Casino, Patricia;Fernandez-Alvarez, Ana;Marina, Alberto
通讯作者：
Marina, Alberto
影响因子：
4.8
作者：
Dutta, R;Inouye, M
通讯作者：
Inouye, M