Solution structure of Rv0569, potent hypoxic signal transduction protein, from Mycobacterium tuberculosis

Abstract

The latent infection is unique characteristic of Mycobacterium tuberculosis to overcome human immune response for its survival. The M. tb develops adaptation to extreme stress conditions to increase the viability, thus easily acquires drug resistance than any other bacteria and maintains a long-term infection status without any symptoms. Rv0569 is a conserved hypothetical protein that overexpresses under dormant state induced by hypoxia, starvation, and medication. To study function and structure in detail, we determined the solution structure of Rv0569 by NMR. NOE and RDC restraints were used to calculate the structure, which was further refined with AMBER. Rv0569 is composed of five antiparallel beta-sheets and one alpha-helix. Rv0569 shows structural similarity with its homolog Rv2302, yet there is a big difference in the orientation of C-terminal alpha-helix between Rv0569 and Rv2302. According to previous studies, Rv0569 might comprise a hypoxia induced operon with the Rv0570 which is located 29 bp downstream of the Rv0569 and Rv0570 plays an important role in the latent infection. From our structure and bioinformatics research, we suggest that Rv0569 contributes to signaling transduction in hypoxic condition by binding with DNA for upregulation of Rv0570 or supporting Rv0570 for binding ATP during dormancy of tuberculosis. (C) 2013 Elsevier Ltd. All rights reserved.