Agrawal Ruchi, Pandey Akancha, Rajankar Mayooreshwar P, Dixit Narendra M, Saini Deepak K
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Department of Chemical Engineering, Indian Institute of Science, Bangalore, India.
Biochem J. 2015 Jul 1;469(1):121-34. doi: 10.1042/BJ20150268. Epub 2015 May 1.
Two-component systems (TCSs), which contain paired sensor kinase and response regulator proteins, form the primary apparatus for sensing and responding to environmental cues in bacteria. TCSs are thought to be highly specific, displaying minimal cross-talk, primarily due to the co-evolution of the participating proteins. To assess the level of cross-talk between the TCSs of Mycobacterium tuberculosis, we mapped the complete interactome of the M. tuberculosis TCSs using phosphotransfer profiling. Surprisingly, we found extensive cross-talk among the M. tuberculosis TCSs, significantly more than that in the TCSs in Escherichia coli or Caulobacter crescentus, thereby offering an alternate to specificity paradigm in TCS signalling. Nearly half of the interactions we detected were significant novel cross-interactions, unravelling a potentially complex signalling landscape. We classified the TCSs into specific 'one-to-one' and promiscuous 'one-to-many' and 'many-to-one' circuits. Using mathematical modelling, we deduced that the promiscuous signalling observed can explain several currently confounding observations about M. tuberculosis TCSs. Our findings suggest an alternative paradigm of bacterial signalling with significant cross-talk between TCSs yielding potentially complex signalling landscapes.
双组分系统（TCSs）由配对的传感器激酶和反应调节蛋白组成，是细菌感知和响应环境信号的主要机制。由于参与其中的蛋白质共同进化，TCSs被认为具有高度特异性，相互干扰极少。为了评估结核分枝杆菌TCSs之间的相互干扰程度，我们利用磷酸转移分析绘制了结核分枝杆菌TCSs的完整相互作用组图谱。令人惊讶的是，我们发现结核分枝杆菌TCSs之间存在广泛的相互干扰，显著多于大肠杆菌或新月柄杆菌中的TCSs，从而为TCS信号传导中的特异性模式提供了另一种可能。我们检测到的相互作用中近一半是显著的新型交叉相互作用，揭示了一个潜在复杂的信号传导格局。我们将TCSs分为特定的“一对一”以及混杂的“一对多”和“多对一”信号通路。通过数学建模，我们推断观察到的混杂信号传导可以解释目前关于结核分枝杆菌TCSs的几个令人困惑的现象。我们的研究结果表明了一种细菌信号传导的替代模式，即TCSs之间存在显著的相互干扰，产生潜在复杂的信号传导格局。
