Cyclic-di-GMP binds to histidine kinase RavS to control RavS-RavR phosphotransfer and regulates the bacterial lifestyle transition between virulence and swimming
Cyclic-di-GMP binds to histidine kinase RavS to control RavS-RavR phosphotransfer and regulates the bacterial lifestyle transition between virulence and swimming
复制标题
Cyclic-di-GMP 与组氨酸激酶 RavS 结合，控制 RavS-RavR 磷酸转移，并调节细菌生活方式在毒力和游动之间的转变
DOI：
10.1371/journal.ppat.1007952
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发表时间：
2019-08-01
期刊：
影响因子：
6.7
通讯作者：
Qian, Wei
中科院分区：
文献类型：
--
作者：
Chengid, Shou-Ting;Wang, Fang-Fang;Qian, Wei
由组氨酸激酶（HK）和反应调节因子（RR）组成的双组分信号系统（TCS）是细菌的主要感觉和反应机制。由于细菌细胞通常编码许多TCS以适应各种生态位，因此TCS的特异性是调节的中心。TCS的特异性由同源HK和RR之间磷酰基转移的能力和速度定义。在这里，我们提供了遗传、酶学和结构数据，证明第二信使环二GMP物理且特异性地结合到RavS，RavS是植物病原性革兰氏阴性细菌野油菜黄单胞菌致病变种的HK。油菜[c-di-GMP]-RavS相互作用通过增强RavS对磷酸化RavR的动力学偏好，显著促进RavS和RavR（一种含有GGDEF-EAL结构域的RR）之间的特异性。[c-di-GMP]-RavS结合有效地降低了RavS的磷酸化水平并负调节细菌游动。有趣的是，RavR的EAL结构域通过降解c-di-GMP然后增加磷酸化RavS的水平来抵消上述调节。因此，RavR作为一个双功能的磷酸汇，精细地控制磷酸化的RavS的水平。这些生化过程相互作用调节RavS-RavR和细菌生活方式转变之间的磷酰基通量。我们的研究结果表明，c-di-GMP作为一种变构效应，动态调节HK和RR之间的特异性。
The two-component signalling system (TCS) comprising a histidine kinase (HK) and a response regulator (RR) is the predominant bacterial sense-and-response machinery. Because bacterial cells usually encode a number of TCSs to adapt to various ecological niches, the specificity of a TCS is in the centre of regulation. Specificity of TCS is defined by the capability and velocity of phosphoryl transfer between a cognate HK and a RR. Here, we provide genetic, enzymology and structural data demonstrating that the second messenger cyclic-di-GMP physically and specifically binds to RavS, a HK of the phytopathogenic, gram-negative bacterium Xanthomonas campestris pv. campestris. The [c-di-GMP]-RavS interaction substantially promotes specificity between RavS and RavR, a GGDEF–EAL domain-containing RR, by reinforcing the kinetic preference of RavS to phosphorylate RavR. [c-di-GMP]-RavS binding effectively decreases the phosphorylation level of RavS and negatively regulates bacterial swimming. Intriguingly, the EAL domain of RavR counteracts the above regulation by degrading c-di-GMP and then increasing the level of phosphorylated RavS. Therefore, RavR acts as a bifunctional phosphate sink that finely controls the level of phosphorylated RavS. These biochemical processes interactively modulate the phosphoryl flux between RavS-RavR and bacterial lifestyle transition. Our results revealed that c-di-GMP acts as an allosteric effector to dynamically modulate specificity between HK and RR.