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NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ

Nature volume 396, pages 88–92 (1998)Cite this article

Abstract

Bacteria live in capricious environments, in which they must continuously sense external conditions in order to adjust their shape, motility and physiology1. The histidine–aspartate phosphorelay signal-transduction system (also known as the two-component system) is important in cellular adaptation to environmental changes in both prokaryotes and lower eukaryotes2,3. In this system, protein histidine kinases function as sensors and signal transducers. The Escherichia coli osmosensor, EnvZ, is a transmembrane protein with histidine kinase activity in its cytoplasmic region2. The cytoplasmic region contains two functional domains4: domain A (residues 223–289) contains the conserved histidine residue (H243), a site of autophosphorylation as well as transphosphorylation to the conserved D55 residue of response regulator OmpR, whereas domain B (residues 290–450) encloses several highly conserved regions (G1, G2, F and N boxes) and is able to phosphorylate H243. Here we present the solution structure of domain B, the catalytic core of EnvZ. This core has a novel protein kinase structure, distinct from the serine/threonine/tyrosine kinase fold, with unanticipated similarities to both heat-shock protein 90 and DNA gyrase B.

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Figure 1: Sequence and structure of the EnvZ catalytic domain.
Figure 2: Identification of the ATP-binding domain in EnvZ and the involvement of N347 in ATP binding.
Figure 3: EnvZ and Hsp90 have a similar fold in their ATP-binding regions.
Figure 4: The EnvZ catalytic domain and DNA gyrase B.

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References

  1. Parkinson, J. S. in Two-Component Signal Transduction(eds Hock, J. A. & Silhavy, T. J.) 9–23 (ASM, Washington, DC, (1995)).

    Google Scholar 

  2. Egger, L. A., Park, H. & Inouye, M. Signal transduction via the histidyl-aspartyl phosphorelay. Genes Cells 2, 167–184 (1997).

    Article  CAS  Google Scholar 

  3. Wirgler-Murphy, S. M. & Saito, H. Two-component signal transducers and MAPK cascades. Trends Biochem. Sci. 22, 172–176 (1997).

    Article  Google Scholar 

  4. Park, H., Saha, S. K. & Inouye, M. Two-domain reconstitution of a functional protein histidine kinase. Proc. Natl Acad. Sci. USA 95, 6728–6732 (1998).

    Article  ADS  CAS  Google Scholar 

  5. Branden, C. & Tooze, J. Introduction to Protein Structure(Garland, New York, (1991)).

    Google Scholar 

  6. Stock, J. B., Surette, M. G., Levit, M. & Park, P. in Two-Component Signal Transduction(eds Hock, J. A. & Silhavy, T. J.) 25–51 (ASM, Washington, DC, (1995)).

    Google Scholar 

  7. Yang, Y. & Inouye, M. Requirement of both kinase and phosphatase activities of an Escherichia coli receptor (Tazl) for ligand-dependent signal transduction. J. Mol. Biol. 231, 335–342 (1993).

    Article  CAS  Google Scholar 

  8. Altschul, S. F.et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).

    Article  CAS  Google Scholar 

  9. Prodromou, C.et al. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90, 65–75 (1997).

    Article  CAS  Google Scholar 

  10. Wigley, D. B.et al. Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351, 624–629 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Dutta, R. & Inouye, M. Reverse phosphotransfer from OmpR to EnvZ in a kinase−/phosphatase+ mutant of EnvZ (EnvZ·N347D), a bifunctional signal transducer of Escherichia coli. J. Biol. Chem. 271, 1424–1429 (1996).

    Article  CAS  Google Scholar 

  12. Min, K.-T.et al. Sigma F, the first compartment-specific transcription factor of B. subtilis, is regulated by anti-sigma factor that is also a protein kinase. Cell 27, 735–742 (1993).

    Article  Google Scholar 

  13. Mizuno, T. Compilation of all genes encoding two-component phosphotransfer signal transducers in the genome of Escherichia coli. DNA Res. 4, 161–168 (1997).

    Article  CAS  Google Scholar 

  14. Ota, I. M. & Varshavsky, A. Ayeast protein similar to bacterial two-component regulators. Science 262, 566–569 (1993).

    Article  ADS  CAS  Google Scholar 

  15. Soncini, F. C. & Groisman, E. A. Two-component regulatory systems can interact to process multiple environmental signals. J. Bacteriol. 178, 6796–6801 (1996).

    Article  CAS  Google Scholar 

  16. Dziejman, M. & Mekalanos, J. J. in Two-Component Signal Transduction(eds Hock, J. A. & Silhavy, T. J.) 305–317 (ASM, Washington, DC, (1995)).

    Google Scholar 

  17. Barrett, J. F.et al. Antibacterial agents that inhibit two-component signal transduction systems. Proc. Natl Acad. Sci. USA 95, 5317–5322 (1998).

    Article  ADS  CAS  Google Scholar 

  18. Nilges, M., Gronenborn, A. M., Brünger, A. T. & Clore, G. M. Determination of three-dimensional structures of proteins by simulated annealing with interproton distance restraints. Application to crambin, potato carboxypeptidase inhibitor and barley serine proteinase inhibitor 2. Protein Eng. 2, 27–38 (1988).

    Article  CAS  Google Scholar 

  19. Brünger, A. T. X-PLOR Version 3.1: A system for X-ray Crystallography and NMR(Yale Univ. Press, New Haven, (1992)).

    Google Scholar 

  20. Kraulis, P. J. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  21. Merritt, E. A. & Murphy, M. E. P. Raster 3D Version 2.0 — a program for photorealistic molecular graphics. Acta Crystallogr. D 50, 869–873 (1994).

    Article  CAS  Google Scholar 

  22. Holdgate, C. A.et al. The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study. Biochemistry 36, 9663–9673 (1997).

    Article  CAS  Google Scholar 

  23. Orengo, C. A., Brown, N. P. & Taylor, W. R. Fast structure alignment for protein databank searching. Proteins 14, 139–167 (1992).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank L. Kay for providing NMR pulse sequences, L. Pearl for the Hsp90-ATP coordinates before PDB release and discussions, and S. Bagby for comments on the manuscript. This work was supported by grants from JSPS (to T.T.) from CREST (to M.K.) from the NIH (to M. Inouye), and from HHMI (to M. Ikura). R.I. and D.L. acknowledge HFSP postdoctoral fellowships. M. Ikura is an HHMI International Research Scholar and MRCC Scientist.

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Author notes

  1. Mark B. Swindells

    Present address: Inpharmatica Ltd, 60 Charlotte Street, London, W1P 2AX, UK

Authors and Affiliations

  1. Center for Tsukuba Advanced Research Alliance and Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, 305-8577, Japan

    Toshiyuki Tanaka & Chieri Tomomori

  2. Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Jersey, 08854, USA

    Soumitra K. Saha, Heiyoung Park, Rinku Dutta, Ling Qin & Masayori Inouye

  3. Division of Molecular and Structural Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, M5G 2M9, Ontario, Canada

    Rieko Ishima, Dingjiang Liu, Kit I. Tong & Mitsuhiko Ikura

  4. Helix Research Institute Inc., Kisarazu, 292-0812, Japan

    Mark B. Swindells

  5. National Institute of Agrobiological Resources, Tsukuba, 305-0856, Japan

    Toshimasa Yamazaki

  6. Department of Chemistry, Tokyo Metropolitan University, Hachioji, 192-0397, Japan

    Akira M. Ono & Masatsune Kainosho

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  1. Toshiyuki Tanaka
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Correspondence to Mitsuhiko Ikura.

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Tanaka, T., Saha, S., Tomomori, C. et al. NMR structure of the histidine kinase domain of the E. coli osmosensor EnvZ. Nature 396, 88–92 (1998). https://doi.org/10.1038/23968

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