Mushtaq Khurram, Sheikh Javaid A, Amir Mohammed, Khan Nargis, Singh Balvinder, Agrewala Javed N
Institute of Microbial Technology, Council of Scientific and Industrial Research Chandigarh, India.
Front Microbiol. 2015 Apr 27;6:351. doi: 10.3389/fmicb.2015.00351. eCollection 2015.
Genes belonging to the same operon are transcribed as a single mRNA molecule in all prokaryotes. The genes of the same operon are presumed to be involved in similar metabolic and physiological processes. Hence, computational analysis of constituent proteins could provide important clues to the functional relationships within the operonic genes. This tends to be more fruitful in the case of Mycobacterium tuberculosis (Mtb), considering the number of hypothetical genes with unknown functions and interacting partners. Dramatic advances in the past decade have increased our knowledge of the mechanisms that tubercle bacilli employ to survive within the host. But the phenomenon of Mtb latency continues to baffle all. Rv2031c belonging to dormancy regulon of Mtb is predominantly expressed during latency, with myriad immunological roles. Thus we attempted to analyze the operon comprising Rv2031c protein to gain insights into its role during latency. In the current study, we have carried out computational analysis of proteins encoded by genes known to be a part of this operon. Our study includes phylogenetic analysis, modeling of protein 3D structures, and protein interaction network analysis. We describe the mechanistic role in the establishment of latency and regulation of DevS-DevR component system. Additionally, we have identified the probable role of these proteins in carbohydrate metabolism, erythromycin tolerance, and nucleotide synthesis. Hence, these proteins can modulate the metabolism of Mtb inside the host cells and can be important for its survival in latency. The functional characterization and interactome of this important operon can give insight into its role during latency along with the exploitation of constituent proteins as drug targets and vaccine candidates.
在所有原核生物中，属于同一操纵子的基因会转录为单个mRNA分子。同一操纵子的基因被认为参与相似的代谢和生理过程。因此，对组成蛋白进行计算分析可为操纵子基因内的功能关系提供重要线索。考虑到结核分枝杆菌（Mtb）中功能未知且相互作用伙伴不明的假设基因数量，这种分析在结核分枝杆菌中往往更有成效。在过去十年中取得的巨大进展增加了我们对结核杆菌在宿主体内存活机制的了解。但Mtb潜伏现象仍然让所有人感到困惑。属于Mtb休眠调节子的Rv2031c在潜伏期间主要表达，具有多种免疫作用。因此，我们试图分析包含Rv2031c蛋白的操纵子，以深入了解其在潜伏期间的作用。在当前研究中，我们对已知是该操纵子一部分的基因所编码的蛋白质进行了计算分析。我们的研究包括系统发育分析、蛋白质三维结构建模和蛋白质相互作用网络分析。我们描述了在休眠建立和DevS-DevR组件系统调节中的机制作用。此外，我们已经确定了这些蛋白质在碳水化合物代谢、红霉素耐受性和核苷酸合成中的可能作用。因此，这些蛋白质可以调节Mtb在宿主细胞内的代谢，对其潜伏生存可能很重要。这个重要操纵子的功能表征和相互作用组可以深入了解其在潜伏期间的作用，同时还可以将组成蛋白开发为药物靶点和疫苗候选物。
