title: Unique N-terminal arm of Mycobacterium tuberculosis PhoP protein plays an unusual role in its regulatory function.
abstract: Mycobacterium tuberculosis PhoP, a master regulator involved in complex lipid biosynthesis and expression of unknown virulence determinants, is composed of an N-terminal receiver domain and a C-terminal effector domain. The two experimentally characterized PhoP orthologs, from Escherichia coli and Salmonella enterica, display vastly different regulatory capabilities. Here, we demonstrate that the 20-residue-long N-terminal arm unique to M. tuberculosis PhoP plays an essential role in the expanded regulatory capabilities of this important regulator. Although the arm is not required for overall structural stability and/or phosphorylation of the PhoP N-domain, strikingly it is essential for phosphorylation-coupled transcription regulation of target genes. Consistent with this view, arm truncation of PhoP is accompanied by a conformational change of the effector domain, presenting a block in activation subsequent to phosphorylation. These results suggest that presence of the arm, unique to this regulator that shares an otherwise highly conserved domain structure with members of the protein family, contributes to the mechanism of inter-domain interactions. Thus, we propose that the N-terminal arm is an adaptable structural feature of M. tuberculosis PhoP, which evolved to fine-tune regulatory capabilities of the transcription factor in response to the changing physiology of the bacilli within its host.
authors: From the CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
authors: Arijit Kumar
authors: AK
authors: Das
authors: Vijjamarri Anil
authors: VA
authors: Kumar
authors: Ritesh Rajesh
authors: RR
authors: Sevalkar
authors: Roohi
authors: R
authors: Bansal
authors: Dibyendu
authors: D
authors: Sarkar
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010755:Organophosphates / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D050505:Mutant Proteins; D010755:Organophosphates; C061064:PhoP protein, Bacteria; C011632:acetyl phosphate; D014357:Trypsin
keywords: DNA-binding Protein; Gene Regulation; Protein-DNA Interaction; Transcription Regulation; Tuberculosis
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