Shrivastava Rashmi, Ghosh Ananta Kumar, Das Amit Kumar
Department of Biotechnology, Indian Institute of Technology-Kharagpur, Kharagpur 721302, India.
Microbiology (Reading). 2009 Mar;155(Pt 3):772-779. doi: 10.1099/mic.0.019059-0.
Two-component signal transduction pathways comprising a histidine kinase and its cognate response regulator play a dominant role in the adaptation of Mycobacterium tuberculosis to its host, and its virulence, pathogenicity and latency. Autophosphorylation occurs at a conserved histidine of the histidine kinase and subsequently the phosphoryl group is transferred to the conserved aspartate of its cognate response regulator. Among the twelve two-component systems of M. tuberculosis, Rv0600c (HK1), Rv0601c (HK2) and Rv0602c (TcrA) are annotated as a unique three-protein two-component system. HK1 contains an ATP-binding domain, and HK2, a novel Hpt mono-domain protein, contains the conserved phosphorylable histidine residue. HK1 and HK2 complement each other's functions. Interactions among different domains of the HK1, HK2 and TcrA proteins were studied using a yeast two-hybrid system. Self-interaction was observed for HK2 but not for HK1 or TcrA. HK2 was found to interact reasonably well with both HK1 and TcrA, but HK1 interacted weakly with TcrA. The conserved aspartate-containing receiver domain of TcrA interacted well with HK2 but not with HK1. These results suggest the existence of a novel signalling mechanism amongst HK1-HK2-TcrA, and a model for this mechanism is proposed.
由组氨酸激酶及其同源反应调节因子组成的双组分信号转导途径在结核分枝杆菌适应宿主及其毒力、致病性和潜伏性方面发挥着主导作用。自磷酸化发生在组氨酸激酶的一个保守组氨酸上，随后磷酸基团转移到其同源反应调节因子的保守天冬氨酸上。在结核分枝杆菌的12个双组分系统中，Rv0600c（HK1）、Rv0601c（HK2）和Rv0602c（TcrA）被注释为一个独特的三蛋白双组分系统。HK1含有一个ATP结合结构域，而HK2是一种新型的Hpt单结构域蛋白，含有保守的可磷酸化组氨酸残基。HK1和HK2相互补充彼此的功能。使用酵母双杂交系统研究了HK1、HK2和TcrA蛋白不同结构域之间的相互作用。观察到HK2存在自相互作用，而HK1或TcrA则没有。发现HK2与HK1和TcrA都有较好的相互作用，但HK1与TcrA的相互作用较弱。TcrA保守的含天冬氨酸的受体结构域与HK2有良好的相互作用，但与HK1没有。这些结果表明在HK1-HK2-TcrA之间存在一种新型信号传导机制，并提出了该机制的模型。
