1887

Abstract

Two-component signal transduction pathways comprising a histidine kinase and its cognate response regulator play a dominant role in the adaptation of 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 , 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.

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2009-03-01
2020-07-05
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References

  1. Aravind L., Ponting C. P.. 1999; The cytoplasmic helical linker domain of receptor histidine kinase and methyl-accepting proteins is common to many prokaryotic signalling proteins. FEMS Microbiol Lett176:111–116
    [Google Scholar]
  2. Bilwes A. M., Alex L. A., Crane B. R., Simon M. I.. 1999; Structure of CheA, a signal transducing histidine kinase. Cell96:131–141
    [Google Scholar]
  3. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglmeier K., Gas S.. other authors 1998; Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature393:537–544
    [Google Scholar]
  4. Dasgupta N., Kapur V., Singh K. K., Das T. K., Sachdeva S., Jyothisri K., Tyagi J. S.. 2000; Characterization of a two-component system, DevR-DevS, of Mycobacterium tuberculosis. Tuber Lung Dis80:141–159
    [Google Scholar]
  5. Ewann F., Jackson M., Pethe K., Cooper A., Mielcarek N., Ensergueix D., Gicquel B., Locht C., Supply P.. 2002; Transient requirement of the PrrA-PrrB two-component system for early intracellular multiplication of Mycobacterium tuberculosis. Infect Immun70:2256–2263
    [Google Scholar]
  6. Fields S., Song O.. 1989; A novel genetic system to detect protein-protein interaction. Nature340:245–246
    [Google Scholar]
  7. Grebe T. W., Stock J. B.. 1999; The histidine protein kinase superfamily. Adv Microb Physiol41:139–227
    [Google Scholar]
  8. Haydel S. E., Benjamin W. H. Jr, Dunlap N. E., Clark-Curtiss J. E.. 2002; Expression, autoregulation, and DNA binding properties of the Mycobacterium tuberculosis TrcR response regulator. J Bacteriol184:2192–2203
    [Google Scholar]
  9. Himpens S., Locht C., Supply P.. 2000; Molecular characterization of the mycobacterial SenX3-RegX3 two-component system: evidence for autoregulation. Microbiology146:3091–3098
    [Google Scholar]
  10. Hoch J. A., Silhavy T. J.. (editors) 1995; Two-component Signal Transduction Washington, DC: American Society for Microbiology;
    [Google Scholar]
  11. Kato M., Shimizu T., Mizuno T., Hakoshima T.. 1999; Structure of the histidine-containing-phosphotransfer (HPt) domain of the anaerobic sensor protein ArcB complexed with the chemotaxis response regulator CheY. Acta Crystallogr D Biol Crystallogr55:1257–1263
    [Google Scholar]
  12. Kern D., Volkman B. F., Luginbuhl P., Nohaile M. J., Kustu S., Wemmer D. E.. 1999; Structure of a transiently phosphorylated switch in bacterial signal transduction. Nature402:894–898
    [Google Scholar]
  13. Khorchid A., Ikura M.. 2006; Bacterial histidine kinase as signal sensor and tranducer. Int J Biochem Cell Biol38:307–312
    [Google Scholar]
  14. Li B., Fields S.. 1993; Identification of mutations in p53 that affect its binding to SV40 T antigen by using the yeast two-hybrid system. FASEB J7:957–963
    [Google Scholar]
  15. Malhotra V., Sharma D., Ramanathan V. D., Shakila H., Saini D. K., Chakravorty S., Das T. K., Li Q., Silver R. F.. other authors 2004; Disruption of response regulator gene, devR, leads to attenuation in virulence of Mycobacterium tuberculosis. FEMS Microbiol Lett231:237–245
    [Google Scholar]
  16. Martínez-Argudo I., Martin-Nieto J., Salinas P., Maldonado R., Drummond M., Contreras A.. 2001; Two-hybrid analysis of domain interactions involving NtrB and NtrC two-component regulators. Mol Microbiol40:169–178
    [Google Scholar]
  17. Miller J. H.. 1972; Experiments in Molecular Genetics Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  18. Mizuno T.. 1997; Compilation of all genes encoding two-component phosphotransfer signal transducers in the genome of Escherichia coli. DNA Res4:161–168
    [Google Scholar]
  19. Morth J. P., Gosmann S., Nowak E., Tucker P. A.. 2005; A novel two-component system found in Mycobacterium tuberculosis. FEBS Lett579:4145–4148
    [Google Scholar]
  20. Parish T., Smith D. A., Roberts G., Betts J., Stoker N. G.. 2003; The SenX3-RegX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiology149:1423–1435
    [Google Scholar]
  21. Perez E., Samper S., Bordas Y., Guilhot C., Gicquel B., Martin C.. 2001; An essential role for PhoP in Mycobacterium tuberculosis virulence. Mol Microbiol41:179–187
    [Google Scholar]
  22. Sherman D. R., Voskuil M., Schnappinger D., Liao R., Harrell M. I., Schoolnik G. K.. 2001; Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding α-crystallin. Proc Natl Acad Sci U S A98:7534–7539
    [Google Scholar]
  23. Shrivastava R., Das D. R., Wiker H. G., Das A. K.. 2006; Functional insights from the molecular modelling of a novel two-component system. Biochem Biophys Res Commun344:1327–1333
    [Google Scholar]
  24. Shrivastava R., Ghosh A. K., Das A. K.. 2007; Probing the nucleotide binding and phosphorylation by the histidine kinase of a novel three-protein two-component system from Mycobacterium tuberculosis. FEBS Lett581:1903–1909
    [Google Scholar]
  25. Steyn A. J. C., Joseph J., Bloom B. R.. 2003; Interaction of the sensor module of Mycobacterium tuberculosis H37Rv KdpD with members of the Lpr family. Mol Microbiol47:1075–1089
    [Google Scholar]
  26. Stock A. M., Robinson V. L., Goudreau P. N.. 2000; Two-component signal transduction. Annu Rev Biochem69:183–215
    [Google Scholar]
  27. Tanaka T., Saha S. K., Tomomori C., Ishima R., Liu D., Tong K. I., Park H., Dutta R., Qin L.. other authors 1998; NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ. Nature396:88–92
    [Google Scholar]
  28. Tomomori C., Tanaka T., Dutta R., Park H., Saha S. K., Zhu Y., Ishima R., Liu D., Tong K. I.. other authors 1999; Solution structure of the homodimeric core domain of Escherichia coli histidine kinase EnvZ. Nat Struct Biol6:729–734
    [Google Scholar]
  29. Tyagi J. S., Sharma D.. 2004; Signal transduction systems of mycobacteria with special reference to M. tuberculosis. Curr Sci86:93–102
    [Google Scholar]
  30. Varughese K. I., Tsigelny I., Zhao H.. 2006; The crystal structure of beryllofluoride Spo0F in complex with the phosphotrasferase Spo0B represents a phosphotransfer pretransition state. J Bacteriol188:4970–4977
    [Google Scholar]
  31. Via L. E., Curcic R., Mudd M. H., Dhandayuthapani S., Ulmer R. J., Deretic V.. 1996; Elements of signal transduction in Mycobacterium tuberculosis: in vitro phosphorylation and in vivo expression of the response regulator MtrA. J Bacteriol178:3314–3321
    [Google Scholar]
  32. Zahrt T. C., Deretic V.. 2001; Mycobacterium tuberculosis signal transduction system required for persistent infections. Proc Natl Acad Sci U S A98:12706–12711
    [Google Scholar]
  33. Zapf J., Sen U., Madhusudan Hoch., A J, Varughese K. I.. 2000; Transient interaction between two phosphorelay proteins trapped in a crystal lattice reveals the mechanism of molecular recognition and phosphotransfer in signal transduction. Structure8:851–862
    [Google Scholar]
  34. Zhang J. H., Xiao G., Gunsalus R. P., Hubbell W. L.. 2003; Phosphorylation triggers domain separation in the DNA binding response regulator NarL. Biochemistry42:2552–2559
    [Google Scholar]
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