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

Cooley, Richard B.; O’Donnell, John P.; Sondermann, Holger

doi:10.7554/elife.21848

Cited by 23 publications

(35 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An additional boost in cyclic nucleotide production was measured when citrate or isocitrate was added to the medium in a strain co-expressing GcbC and LapD, indicating that the enhanced GcbC-LapD interaction also enhanced DGC activity. Furthermore, recent work from the Sondermann lab (25) identified a LapD dimer-of-dimers as a c-di-GMP- and LapG-bound state, which could serve as an interaction platform or “receptor basket” for GcbC, thereby forming a large LapD-LapG-GcbC-c-di-GMP signaling complex (Fig. 5C).…”

Section: Resultsmentioning

confidence: 97%

See 1 more Smart Citation

Ligand-Mediated Biofilm Formation via Enhanced Physical Interaction Between a Diguanylate Cyclase and Its Receptor

Giacalone

Smith

Collins

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

The second messenger, cyclic dimeric GMP (c-di-GMP) regulates biofilm formation for many bacteria. The binding of c-d¡-GMP by the inner-membrane protein LapD controls biofilm formation, and the LapD receptor is central to a complex network of c-di-GMP-mediated biofilm formation. In this study, we examine how c-di-GMP signaling specificity by a diguanylate cyclase (DGC), GcbC, is achieved via interactions with the LapD receptor and by small ligand sensing via GcbC’s calcium channel chemotaxis (CACHE) domain. We provide evidence that biofilm formation is stimulated by the environmentally relevant organic acid citrate (and a related compound, isocitrate) in a GcbC-dependent manner through enhanced GcbC-LapD interaction, which results in increased LapA localization to the cell surface. Furthermore, GcbC shows little ability to synthesize c-di-GMP in isolation. However, when LapD is present GcbC activity is significantly enhanced ~8-fold, indicating that engaging the LapD receptor stimulates the activity of this DGC; citrate-enhanced GcbC-LapD interaction further stimulates c-di-GMP synthesis. We propose that the l-site of GcbC serves two roles beyond allosteric control of this enzyme: promoting GcbC-LapD interaction and stabilizing the active conformation of GcbC in the GcbC-LapD complex. Finally, given that LapD can interact with a dozen different DGCs of P. fluorescens, many of which have ligand-binding domains, the ligand-mediated enhanced signaling via LapD-GcbC interaction described here is likely a conserved mechanism of signaling in this network. Consistent with this idea, we identify a second example of ligand-mediated enhancement of DGC-LapD interaction that promotes biofilm formation.ImportanceIn many bacteria, dozens of enzymes produce the dinucleotide signal c-di-GMP, however it is unclear how undesired crosstalk is mitigated in the context of this soluble signal, and how c-di-GMP signaling is regulated by environmental inputs. We demonstrate that GcbC, a DGC, shows little ability to synthesize c-d¡-GMP in the absence of its cognate receptor LapD; GcbC-LapD interaction enhances c-di-GMP synthesis by GcbC, likely mediated by the l-site of GcbC. We further show evidence for a ligand-mediated mechanism of signaling specificity via increased physical interaction of a DGC with its cognate receptor. We envision a scenario wherein a “cloud” of weakly active DGCs can increase their activity by specific interaction with their receptor in response to appropriate environmental signals, concomitantly boosting c-di-GMP production, ligand-specific signaling and biofilm formation.

show abstract

Section: Resultsmentioning

confidence: 97%

“…P<0.01 (**); P<0.001 (***). (C) A model of a GcbC, LapD and LapG “basket” signaling complex (25). In this model, the DGC- and PDE-like domains are indicated by the GGDEF and EAL residues typically associated with the active enzymes; we showed previously that these domains of LapD are not active.…”

Section: Resultsmentioning

confidence: 99%

Ligand-Mediated Biofilm Formation via Enhanced Physical Interaction Between a Diguanylate Cyclase and Its Receptor

Giacalone

Smith

Collins

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since the HAMP input signal is the output signal of a corresponding TM domain, understanding HAMP function would also be beneficial for studying TM signaling. We note that the signal can also be transduced in the other direction, from the HAMP to the TM domain …”

Section: Hamp Domain: Convertor From Piston To Helical Rotationmentioning

confidence: 98%

Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

Gushchin

Gordeliy

2017

BioEssays

View full text Add to dashboard Cite

Allosteric and transmembrane (TM) signaling are among the major questions of structural biology. Here, we review and discuss signal transduction in four-helical TM bundles, focusing on histidine kinases and chemoreceptors found in two-component systems. Previously, piston, scissors, and helical rotation have been proposed as the mechanisms of TM signaling. We discuss theoretically possible conformational changes and examine the available experimental data, including the recent crystallographic structures of nitrate/nitrite sensor histidine kinase NarQ and phototaxis system NpSRII:NpHtrII. We show that TM helices can flex at multiple points and argue that the various conformational changes are not mutually exclusive, and often are observed concomitantly, throughout the TM domain or in its part. The piston and scissoring motions are the most prominent motions in the structures, but more research is needed for definitive conclusions.

show abstract

“…CdrA is the passenger protein of a two-partner secretion system (also known as type Vb secretion system) and specifically interacts with the matrix exopolysaccharide Psl polymers, stabilizing matrix integrity and biofilm structure (Borlee et al, 2010). As observed with LapA, the LapG protein functions as a periplasmic protease that controls proteolysis of CdrA in response to low cellular c-di-GMP levels, and by doing so, allows the release of CdrA from the outer membrane to promote biofilm dispersal Cooley et al, 2016).…”

Section: Effectors Promoting Biofilm Dispersalmentioning

confidence: 99%

Biofilm dispersal: multiple elaborate strategies for dissemination of bacteria with unique properties

Guilhen

Forestier

Balestrino

2017

Molecular Microbiology

158

143

View full text Add to dashboard Cite

Summary In most environments, microorganisms evolve in a sessile mode of growth, designated as biofilm, which is characterized by cells embedded in a self‐produced extracellular matrix. Although a biofilm is commonly described as a “cozy house” where resident bacteria are protected from aggression, bacteria are able to break their biofilm bonds and escape to colonize new environments. This regulated process is observed in a wide variety of species; it is referred to as biofilm dispersal, and is triggered in response to various environmental and biological signals. The first part of this review reports the main regulatory mechanisms and effectors involved in biofilm dispersal. There is some evidence that dispersal is a necessary step between the persistence of bacteria inside biofilm and their dissemination. In the second part, an overview of the main methods used so far to study the dispersal process and to harvest dispersed bacteria was provided. Then focus was on the properties of the biofilm‐dispersed bacteria and the fundamental role of the dispersal process in pathogen dissemination within a host organism. In light of the current body of knowledge, it was suggested that dispersal acts as a potent means of disseminating bacteria with enhanced colonization properties in the surrounding environment.

show abstract

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

Cited by 23 publications

References 74 publications

Ligand-Mediated Biofilm Formation via Enhanced Physical Interaction Between a Diguanylate Cyclase and Its Receptor

Ligand-Mediated Biofilm Formation via Enhanced Physical Interaction Between a Diguanylate Cyclase and Its Receptor

Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

Biofilm dispersal: multiple elaborate strategies for dissemination of bacteria with unique properties

Contact Info

Product

Resources

About