computational analysis of the esx-1 region of mycobacterium tuberculosis insights into the mechanism of type vii secretion system计算分析esx-1地区结核分枝杆菌的见解vii型分泌系统的机制.pdf

Computational Analysis of the ESX-1 Region of Mycobacterium tuberculosis: Insights into the Mechanism of Type VII Secretion System Chandrani Das., Tarini Shankar Ghosh., Sharmila S Mande* Bio-sciences R D Division, Tata Consultancy ServicesInnovation Labs, Tata Consultancy Services Ltd, Hyderabad, Andhra Pradesh, India Abstract Type VII secretion system (T7SS) is a recent discovery in bacterial secretion systems. First identified in Mycobacterium tuberculosis, this secretion system has later been reported in organisms belonging to the Actinomycetales order and even to distant phyla like Firmicutes. The genome of M. tuberculosis H37Rv contains five gene clusters that have evolved through gene duplication events and include components of the T7SS secretion machinery. These clusters are called ESAT-6 secretion system (ESX) 1 through 5. Out of these, ESX-1 has been the most widely studied region because of its pathological importance. In spite of this, the overall mechanism of protein translocation through ESX-1 secretion machinery is not clearly understood. Specifically, the structural components contributing to the translocation through the mycomembrane have not been characterized yet. In this study, we have carried out a comprehensive in silico analysis of the genes known to be involved in ESX-1 secretion pathway and identified putative proteins having high probability to be associated with this particular pathway. Our study includes analysis of phylogenetic profiles, identification of domains, transmembrane helices, 3D folds, signal peptides and prediction of protein-protein associations. Based on our analysis, we could assign probable novel functions to a few of the ESX-1 components. Additionally, we have identified a few proteins with probable role in the initial activation and formation of mycomembrane transl