title: Intra- and intermolecular domain interactions among novel two-component system proteins coded by Rv0600c, Rv0601c and Rv0602c of Mycobacterium tuberculosis.
abstract: Two-component signal transduction pathways comprising a histidine kinase and its cognate response regulator play a dominant role in the adaptation of Mycobacterium tuberculosis to its host, and its virulence, pathogenicity and latency. Autophosphorylation occurs at a conserved histidine of the histidine kinase and subsequently the phosphoryl group is transferred to the conserved aspartate of its cognate response regulator. Among the twelve two-component systems of M. tuberculosis, Rv0600c (HK1), Rv0601c (HK2) and Rv0602c (TcrA) are annotated as a unique three-protein two-component system. HK1 contains an ATP-binding domain, and HK2, a novel Hpt mono-domain protein, contains the conserved phosphorylable histidine residue. HK1 and HK2 complement each other's functions. Interactions among different domains of the HK1, HK2 and TcrA proteins were studied using a yeast two-hybrid system. Self-interaction was observed for HK2 but not for HK1 or TcrA. HK2 was found to interact reasonably well with both HK1 and TcrA, but HK1 interacted weakly with TcrA. The conserved aspartate-containing receiver domain of TcrA interacted well with HK2 but not with HK1. These results suggest the existence of a novel signalling mechanism amongst HK1-HK2-TcrA, and a model for this mechanism is proposed.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology-Kharagpur, Kharagpur 721302, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Shrivastava
authors.affiliation: Department of Biotechnology, Indian Institute of Technology-Kharagpur, Kharagpur 721302, India.
authors.forename: Ananta Kumar
authors.initials: AK
authors.lastname: Ghosh
authors.affiliation: Department of Biotechnology, Indian Institute of Technology-Kharagpur, Kharagpur 721302, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Das
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D000071677:Histidine Kinase; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins; D011494:Protein Kinases; D000071677:Histidine Kinase