A Symphony of Cyclases: Specificity in Diguanylate Cyclase Signaling

Annu Rev Microbiol. 2017 Sep 8;71:179-195. doi: 10.1146/annurev-micro-090816-093325. Epub 2017 Jun 23.


Cyclic diguanylate (c-di-GMP) is a near universal signaling molecule produced by diguanylate cyclases that can direct a variety of bacterial behaviors. A major area of research over the last several years has been aimed at understanding how a cell with dozens of diguanylate cyclases can deploy a given subset of them to produce a desired phenotypic outcome without undesired cross talk between c-di-GMP-dependent systems. Several models have been put forward to address this question, including specificity of cyclase activation, tuned binding constants of effector proteins, and physical interaction between cyclases and effectors. Additionally, recent evidence has suggested that there may be a link between the catalytic state of a cyclase and its physical contact with an effector. This review highlights several key studies, examines the proposed global and local models of c-di-GMP signaling specificity in bacteria, and attempts to identify the most fruitful steps that can be taken to better understand how dynamic networks of sibling cyclases and effector proteins result in sensible outputs that govern cellular behavior.

Keywords: biofilms; c-di-GMP; cyclic diguanylate; diguanylate cyclase; signaling specificity.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacteria / enzymology*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Models, Biological
  • Phosphorus-Oxygen Lyases / metabolism*
  • Protein Binding
  • Signal Transduction*
  • Substrate Specificity


  • Escherichia coli Proteins
  • bis(3',5')-cyclic diguanylic acid
  • Phosphorus-Oxygen Lyases
  • diguanylate cyclase
  • Cyclic GMP