Conformational dynamics of the essential sensor histidine kinase WalK.
Conformational dynamics of the essential sensor histidine kinase WalK.
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重要传感器组氨酸激酶 WalkK 的构象动力学
DOI：
10.1107/s2059798317013043
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发表时间：
2017-10-01
期刊：
影响因子：
--
通讯作者：
Han A
中科院分区：
文献类型：
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作者：
Cai Y;Su M;Ahmad A;Hu X;Sang J;Kong L;Chen X;Wang C;Shuai J;Han A
WalK的不同构象揭示了传感器组氨酸激酶结构作为多功能性的分子基础的内在动力学性质。双组分系统（TCS）是细菌响应环境胁迫信号转导的关键元件。TCS通常由传感器组氨酸激酶（SK）及其同源反应调节因子（RR）组成。许多SK表现出自激酶、磷酸转移酶和磷酸酶活性，其通过磷酸化和去磷酸化循环调节RR活性。然而，SK如何执行不同的酶活性知之甚少。在这里，几个晶体结构的最小催化区的WalK，一个必要的SK从植物乳杆菌，其同源物VicK从变形链球菌的序列同一性为60%，提出。WalK在ATP或ADP存在下采用不对称的闭合结构，其中CA结构域之一位于靠近DHp结构域的位置，从而导致ATP/ADP的β-和γ-磷酸与DHp结构域中可磷酸化组氨酸的α-氮形成氢键，但不与δ-氮形成氢键。此外，ATP/ADP结合状态下的DHp结构域具有与CA结构域的重新定位协调的25.7°不对称螺旋弯曲;这些过程是相互排斥的，并且响应于可能由上游信号调节的螺旋度变化而交替。然而，在缺乏ATP或ADP的情况下，WalK采用完全对称的开放结构，其DHp结构域位于两个向外延伸的CA结构域之间。总之，WalK的这些结构揭示了SK结构作为多功能性的分子基础的内在动力学性质。
The different conformations of WalK reveal the intrinsic dynamic properties of a sensor histidine kinase structure as a molecular basis for multifunctionality. Two-component systems (TCSs) are key elements in bacterial signal transduction in response to environmental stresses. TCSs generally consist of sensor histidine kinases (SKs) and their cognate response regulators (RRs). Many SKs exhibit autokinase, phosphoryltransferase and phosphatase activities, which regulate RR activity through a phosphorylation and dephosphorylation cycle. However, how SKs perform different enzymatic activities is poorly understood. Here, several crystal structures of the minimal catalytic region of WalK, an essential SK from Lactobacillus plantarum that shares 60% sequence identity with its homologue VicK from Streptococcus mutans, are presented. WalK adopts an asymmetrical closed structure in the presence of ATP or ADP, in which one of the CA domains is positioned close to the DHp domain, thus leading both the β- and γ-phosphates of ATP/ADP to form hydrogen bonds to the ∊- but not the δ-nitrogen of the phosphorylatable histidine in the DHp domain. In addition, the DHp domain in the ATP/ADP-bound state has a 25.7° asymmetrical helical bending coordinated with the repositioning of the CA domain; these processes are mutually exclusive and alternate in response to helicity changes that are possibly regulated by upstream signals. In the absence of ATP or ADP, however, WalK adopts a completely symmetric open structure with its DHp domain centred between two outward-reaching CA domains. In summary, these structures of WalK reveal the intrinsic dynamic properties of an SK structure as a molecular basis for multifunctionality.