Coincidence detection and bi-directional transmembrane signaling control a bacterial second messenger receptor
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.
Article and author information
Author details
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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