1. Structural Biology and Molecular Biophysics
  2. Microbiology and Infectious Disease
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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
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Cite this article as: eLife 2016;5:e21848 doi: 10.7554/eLife.21848


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.

Article and author information

Author details

  1. Richard B Cooley

    Department of Biochemistry and Biophysics, Oregon State University, Corvallis, United States
    For correspondence
    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
    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


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.

Reviewing Editor

  1. Jon Clardy, Harvard Medical School, United States

Publication history

  1. Received: September 27, 2016
  2. Accepted: December 20, 2016
  3. Accepted Manuscript published: December 21, 2016 (version 1)
  4. Version of Record published: January 12, 2017 (version 2)


© 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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