Molecular chaperones are a conserved family of proteins that are over-expressed in response to heat and other stresses. The regulation of expression of chaperone proteins plays a vital role in pathogenesis of various bacterial pathogens. In M. tuberculosis, HrcA and HspR negatively regulate heat shock protein operons by binding to their cognate DNA elements, CIRCE and HAIR respectively. In this study, we show that M. tuberculosis HrcA is able to bind to its cognate CIRCE DNA element present in the upstream regions of groES and groEL2 operons only with the help of other protein(s). It is also demonstrated that M. tuberculosis HrcA binds to a CIRCE like DNA element present in the upstream region of hrcA gene suggesting its auto-regulatory nature. In addition, we report the presence of a putative HAIR element in the upstream region of groES operon and demonstrate the binding of HspR to it. In vitro, HrcA inhibited the DNA binding activity of HspR in a dose-dependent manner. The current study demonstrates that M. tuberculosis HrcA requires other protein(s) to function, and the heat shock protein expression in M. tuberculosis is negatively regulated jointly by HrcA and HspR.

中文翻译：

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HrcA在结核分枝杆菌热休克调节中的功能机制。

分子伴侣蛋白是保守的蛋白质家族，其响应热和其他压力而过表达。伴侣蛋白表达的调节在各种细菌病原体的发病机理中起着至关重要的作用。在结核分枝杆菌中，HrcA和HspR通过分别与它们的同源DNA元件CIRCE和HAIR结合而负调控热休克蛋白操纵子。在这项研究中，我们表明结核分枝杆菌HrcA仅在其他蛋白质的帮助下才能与groES和groEL2操纵子上游区域中存在的同源CIRCE DNA元件结合。还证明结核分枝杆菌HrcA与hrcA基因上游区域中存在的CIRCE样DNA元件结合，表明其具有自动调节性质。此外，我们报告了在groES操纵子上游区域存在假定的HAIR元件，并证明了HspR与其结合。在体外，HrcA以剂量依赖性方式抑制HspR的DNA结合活性。当前的研究表明，结核分枝杆菌HrcA需要其他蛋白质才能发挥功能，而结核分枝杆菌中的热激蛋白表达受HrcA和HspR共同负调控。