1887

Abstract

Many biological signalling pathways have evolved to produce responses to environmental signals that are robust to fluctuations in protein copy number and noise. Whilst beneficial for biology, this robustness can be problematic for synthetic biologists wishing to re-engineer and subsequently tune the response of a given system. Here we show that the well-characterized EnvZ/OmpR two-component signalling system from possesses one such robust step response. However, the synthetic addition of just a single component into the system, an extra independently controllable phosphatase, can change this behaviour to become graded and tunable, and even show adaptation. Our approach introduces a new design principle which can be implemented simply in engineering and redesigning fast signal transduction pathways for synthetic biology.

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/content/journal/micro/10.1099/mic.0.066324-0
2013-07-01
2020-01-22
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References

  1. Alves R., Savageau M. A..( 2003;). Comparative analysis of prototype two-component systems with either bifunctional or monofunctional sensors: differences in molecular structure and physiological function. Mol Microbiol48:25–51 [CrossRef][PubMed]
    [Google Scholar]
  2. Bashor C. J., Horwitz A. A., Peisajovich S. G., Lim W. A..( 2010;). Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems. Annu Rev Biophys39:515–537 [CrossRef][PubMed]
    [Google Scholar]
  3. Batchelor E., Goulian M..( 2003;). Robustness and the cycle of phosphorylation and dephosphorylation in a two-component regulatory system. Proc Natl Acad Sci U S A100:691–696 [CrossRef][PubMed]
    [Google Scholar]
  4. Batchelor E., Walthers D., Kenney L. J., Goulian M..( 2005;). The Escherichia coli CpxA-CpxR envelope stress response system regulates expression of the porins ompF and ompC.. J Bacteriol187:5723–5731 [CrossRef][PubMed]
    [Google Scholar]
  5. Casino P., Rubio V., Marina A..( 2009;). Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction. Cell139:325–336 [CrossRef][PubMed]
    [Google Scholar]
  6. Forst S. A., Roberts D. L..( 1994;). Signal transduction by the EnvZ-OmpR phosphotransfer system in bacteria. Res Microbiol145:363–373 [CrossRef][PubMed]
    [Google Scholar]
  7. Jin T., Inouye M..( 1993;). Ligand binding to the receptor domain regulates the ratio of kinase to phosphatase activities of the signaling domain of the hybrid Escherichia coli transmembrane receptor, Taz1. J Mol Biol232:484–492 [CrossRef][PubMed]
    [Google Scholar]
  8. Jin T., Inouye M..( 1994;). Transmembrane signaling: mutational analysis of the cytoplasmic linker region of Taz1-1, a Tar-EnvZ chimeric receptor in Escherichia coli. J Mol Biol244:477–481 [CrossRef][PubMed]
    [Google Scholar]
  9. Kenney L. J..( 1997;). Kinase activity of EnvZ, an osmoregulatory signal transducing protein of Escherichia coli. Arch Biochem Biophys346:303–311 [CrossRef][PubMed]
    [Google Scholar]
  10. King S. T., Kenney L. J..( 2007;). Application of fluorescence resonance energy transfer to examine EnvZ/OmpR interactions. Methods Enzymol422:352–360 [CrossRef][PubMed]
    [Google Scholar]
  11. Lim W. A..( 2010;). Designing customized cell signalling circuits. Nat Rev Mol Cell Biol11:393–403 [CrossRef][PubMed]
    [Google Scholar]
  12. Michalodimitrakis K. M., Sourjik V., Serrano L..( 2005;). Plasticity in amino acid sensing of the chimeric receptor Taz. Mol Microbiol58:257–266 [CrossRef][PubMed]
    [Google Scholar]
  13. Miller J. H..( 1992;). A Short Course in Bacterial Genetics: A Laboratory Manual and Handbook for Escherichia coli and Related Bacteria Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  14. Qin L., Yoshida T., Inouye M..( 2001;). The critical role of DNA in the equilibrium between OmpR and phosphorylated OmpR mediated by EnvZ in Escherichia coli. Proc Natl Acad Sci U S A98:908–913[PubMed]
    [Google Scholar]
  15. Sato M., Machida K., Arikado E., Saito H., Kakegawa T., Kobayashi H..( 2000;). Expression of outer membrane proteins in Escherichia coli growing at acid pH. Appl Environ Microbiol66:943–947 [CrossRef][PubMed]
    [Google Scholar]
  16. Shinar G., Feinberg M..( 2010;). Structural sources of robustness in biochemical reaction networks. Science327:1389–1391 [CrossRef][PubMed]
    [Google Scholar]
  17. Shinar G., Milo R., Martínez M. R., Alon U..( 2007;). Input output robustness in simple bacterial signaling systems. Proc Natl Acad Sci U S A104:19931–19935 [CrossRef][PubMed]
    [Google Scholar]
  18. Utsumi R., Brissette R. E., Rampersaud A., Forst S. A., Oosawa K., Inouye M..( 1989;). Activation of bacterial porin gene expression by a chimeric signal transducer in response to aspartate. Science245:1246–1249 [CrossRef][PubMed]
    [Google Scholar]
  19. Wadhams G. H., Armitage J. P..( 2004;). Making sense of it all: bacterial chemotaxis. Nat Rev Mol Cell Biol5:1024–1037 [CrossRef][PubMed]
    [Google Scholar]
  20. Wagner S., Bader M. L., Drew D., de Gier J. W..( 2006;). Rationalizing membrane protein overexpression. Trends Biotechnol24:364–371 [CrossRef][PubMed]
    [Google Scholar]
  21. Wagner S., Baars L., Ytterberg A. J., Klussmeier A., Wagner C. S., Nord O., Nygren P. A., van Wijk K. J., de Gier J. W..( 2007;). Consequences of membrane protein overexpression in Escherichia coli. Mol Cell Proteomics6:1527–1550 [CrossRef][PubMed]
    [Google Scholar]
  22. Wolfe A. J..( 2005;). The acetate switch. Microbiol Mol Biol Rev69:12–50 [CrossRef][PubMed]
    [Google Scholar]
  23. Yi T. M., Huang Y., Simon M. I., Doyle J..( 2000;). Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci U S A97:4649–4653 [CrossRef][PubMed]
    [Google Scholar]
  24. Yoshida T., Cai S., Inouye M..( 2002;). Interaction of EnvZ, a sensory histidine kinase, with phosphorylated OmpR, the cognate response regulator. Mol Microbiol46:1283–1294 [CrossRef][PubMed]
    [Google Scholar]
  25. Yoshida T., Qin L., Egger L. A., Inouye M..( 2006;). Transcription regulation of ompF and ompC by a single transcription factor, OmpR. J Biol Chem281:17114–17123 [CrossRef][PubMed]
    [Google Scholar]
  26. Yoshida T., Phadtare S., Inouye M..( 2007;). The design and development of Tar-EnvZ chimeric receptors. Methods Enzymol423:166–183 [CrossRef][PubMed]
    [Google Scholar]
  27. Zhu Y., Qin L., Yoshida T., Inouye M..( 2000;). Phosphatase activity of histidine kinase EnvZ without kinase catalytic domain. Proc Natl Acad Sci U S A97:7808–7813 [CrossRef][PubMed]
    [Google Scholar]
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