1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease

Coincidence detection and bi-directional transmembrane signaling control a bacterial second messenger receptor

  1. Richard B Cooley  Is a corresponding author
  2. John P O'Donnell
  3. Holger Sondermann  Is a corresponding author
  1. Oregon State University, United States
  2. Cornell University, United States
https://doi.org/10.7554/eLife.21848
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  1. Richard B Cooley
  2. John P O'Donnell
  3. Holger Sondermann
(2016)
Coincidence detection and bi-directional transmembrane signaling control a bacterial second messenger receptor
eLife 5:e21848.
https://doi.org/10.7554/eLife.21848
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Abstract

The second messenger c-di-GMP regulates biofilm formation, a physiological adaptation process in bacteria, via a widely conserved signaling node comprising a prototypical transmembrane receptor for c-di-GMP, LapD, and a cognate periplasmic protease, LapG. Previously, we reported a structure-function study of a soluble LapD-LapG complex, establishing conformational changes in the receptor that lead to c-di-GMP-dependent protease recruitment (Chatterjee et al., 2014). This work also revealed a basal affinity of c-di-GMP-unbound receptor for LapG, the relevance of which remained enigmatic. Here, we elucidate the structural basis of coincidence detection that relies on both c-di-GMP and LapG binding to LapD for receptor activation. The data indicate that the high-affinity state for LapG relies on the formation of a receptor dimer-of-dimers, rather than a simple conformational change within dimeric LapD. The proposed mechanism provides a rationale of how external proteins can regulate receptor function and may also apply to c-di-GMP-metabolizing enzymes akin to LapD.

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Author details

  1. Richard B Cooley

    Department of Biochemistry and Biophysics, Oregon State University, Corvallis, United States
    For correspondence
    cooleyr@oregonstate.edu
    Competing interests
    The authors declare that no competing interests exist.

  2. John P O'Donnell

    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Holger Sondermann

    Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, United States
    For correspondence
    hs293@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2211-6234

Funding

National Institute of Allergy and Infectious Diseases (R01-AI097307)

  • Holger Sondermann

National Institute of General Medical Sciences (F32-GM108440)

  • Richard B Cooley

National Institute of General Medical Sciences (T32-GM008500)

  • John P O'Donnell

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2016, Cooley et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Richard B Cooley
  2. John P O'Donnell
  3. Holger Sondermann
(2016)
Coincidence detection and bi-directional transmembrane signaling control a bacterial second messenger receptor
eLife 5:e21848.
https://doi.org/10.7554/eLife.21848

Share this article

https://doi.org/10.7554/eLife.21848

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Further reading

    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP

    Debashree Chatterjee, Richard B Cooley ... Holger Sondermann
    Research Article

    Stable surface adhesion of cells is one of the early pivotal steps in bacterial biofilm formation, a prevalent adaptation strategy in response to changing environments. In Pseudomonas fluorescens, this process is regulated by the Lap system and the second messenger cyclic-di-GMP. High cytoplasmic levels of cyclic-di-GMP activate the transmembrane receptor LapD that in turn recruits the periplasmic protease LapG, preventing it from cleaving a cell surface-bound adhesin, thereby promoting cell adhesion. In this study, we elucidate the molecular basis of LapG regulation by LapD and reveal a remarkably sensitive switching mechanism that is controlled by LapD's HAMP domain. LapD appears to act as a coincidence detector, whereby a weak interaction of LapG with LapD transmits a transient outside-in signal that is reinforced only when cyclic-di-GMP levels increase. Given the conservation of key elements of this receptor system in many bacterial species, the results are broadly relevant for cyclic-di-GMP- and HAMP domain-regulated transmembrane signaling.