title: Phosphorylation of PhoP Protein Plays Direct Regulatory Role in Lipid Biosynthesis of Mycobacterium tuberculosis.
creator: Goyal, Rajni
creator: Das, Arijit Kumar
creator: Singh, Ranjeet
creator: Singh, Pradip Kumar
creator: Korpole, Suresh
creator: Sarkar, Dibyendu
subject: QR Microbiology
description: Mycobacterium tuberculosis PhoP is essential for virulence and intracellular growth of the tubercle bacilli. Genetic evidence suggests that PhoP regulates complex lipid biosynthesis, and absence of some of these lipid molecules in a phoP mutant partly accounts for its attenuated growth in macrophages and/or mice. To investigate the mechanism of regulation, here we demonstrate the essentiality of phosphorylation of PhoP in the regulation of complex lipid biosynthesis. We show that phosphorylated PhoP activates transcription of pks2 and msl3, gene(s) encoding polyketide β-ketoacyl synthases through direct DNA binding at the upstream regulatory region(s) of the target genes. Our results identify the genetic determinants recognized by PhoP and show that activation of target genes requires interaction(s) of the phosphorylated regulator at the cognate binding sites. The fact that these sites within the regulatory region of respective genes do not bind in vitro with either unphosphorylated or phosphorylation-deficient PhoP protein is consistent with phosphorylation-dependent assembly of the transcription initiation complex leading to in vivo transcriptional activation. Together, these results reveal so far unknown molecular mechanisms of how PhoP contributes to M. tuberculosis cell wall composition by regulating complex lipid biosynthesis.
publisher: ASBMB
date: 2011-12-30
type: Article
type: PeerReviewed
format: application/pdf
identifier: http://crdd.osdd.net/open/692/1/sarkar2011.pdf
relation: http://www.jbc.org/content/286/52/45197
identifier:   Goyal, Rajni and Das, Arijit Kumar and Singh, Ranjeet and Singh, Pradip Kumar and Korpole, Suresh and Sarkar, Dibyendu  (2011) Phosphorylation of PhoP Protein Plays Direct Regulatory Role in Lipid Biosynthesis of Mycobacterium tuberculosis.  The Journal of biological chemistry, 286 (52).  pp. 45197-208.  ISSN 1083-351X     
relation: http://crdd.osdd.net/open/692/