Solution structure of the PhoP DNA-binding domain from Mycobacterium tuberculosis
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The bacterial pathogen Mycobacterium tuberculosis (MTB) causes tuberculosis resulting annually in ~1.5 million fatalities world-wide (WHO 2014). During the initial stage of an infection, MTB is inhaled and transported to the lungs where it is believed to infect alveolar macrophages (Russell et al. 2010). Once inside the macrophage, MTB encounters new oxidative and acidic stressors, and alters its gene expression profile to cope with this new environment (Gonzalo-Asensio et al. 2008). The MTB PhoP-PhoR (PhoPR) two-component system plays a critical role in microbial adaptation. In this system, environmental signals received by the membrane associated PhoR protein trigger its autophosphorylation. PhoR then transfers the phosphate to the cytoplasmic PhoP response regulator, which in its phosphorylated state sequence specifically binds DNA with high affinity (Pathak et al. 2010). Several studies have shown that PhoP is required for MTB virulence (Perez et al. 2001;...
KeywordsNOESY Spectrum Distance Restraint Chemical Shift Assignment Dihedral Angle Restraint Side Chain Chemical Shift
We would like to thank Albert H. Chan and Megan Sjodt for guidance throughout the structure determination process. We would like to thank Dr. Robert Peterson for assistance with NMR experiments. This work was supported by the National Institutes of Health grant AI52217 to RTC. R. M. was supported by a Cellular and Molecular Biology Training Grant (Ruth L. Kirschstein National Research Service Award GM007185). D. S. was supported by Raman Research Fellowship from the Council of Scientific and Industrial Research (CSIR), Government of India. B. R. A. was supported by a Whitcome Predoctoral Training Grant, University of California—Los Angeles, Molecular Biology Institute. This material is based upon work supported by the US. Department of Energy Office of Science, Office of Biological and Environmental Research program under Award Number DE-FC02-02ER63421.
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Conflict of interest
The authors declare no conflict of interest.
Research does not involve human participants and/or animals.
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