A cyclic-di-GMP Receptor Required for Bacterial Exopolysaccharide Production

Mol Microbiol. 2007 Sep;65(6):1474-84. doi: 10.1111/j.1365-2958.2007.05879.x.

Abstract

Bis-(3',5')-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been shown to be a global regulatory molecule that modulates the reciprocal responses of bacteria to activate either virulence pathways or biofilm formation. The mechanism of c-di-GMP signal transduction, including recognition of c-di-GMP and subsequent phenotypic regulation, remain largely uncharacterized. The key components of these regulatory pathways are the various adaptor proteins (c-di-GMP receptors). There is compelling evidence suggesting that, in addition to PilZ domains, there are other unidentified c-di-GMP receptors. Here we show that the PelD protein of Pseudomonas aeruginosa is a novel c-di-GMP receptor that mediates c-di-GMP regulation of PEL polysaccharide biosynthesis. Analysis of PelD orthologues identified a number of conserved residues that are required for c-di-GMP binding as well as synthesis of the PEL polysaccharide. Secondary structure similarities of PelD to the inhibitory site of diguanylate cyclase suggest that a common fold can act as a platform to bind c-di-GMP. The combination of a c-di-GMP binding site with a variety of output signalling motifs within one protein domain provides an explanation for the specificity for different cellular responses to this regulatory dinucleotide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / metabolism
  • Biofilms
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Conserved Sequence
  • Escherichia coli Proteins
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation / genetics
  • Operon / genetics
  • Phenotype
  • Phosphorus-Oxygen Lyases / metabolism
  • Polysaccharides, Bacterial / biosynthesis*
  • Protein Binding
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa / metabolism*
  • Pseudomonas aeruginosa / physiology
  • Signal Transduction

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • Intracellular Signaling Peptides and Proteins
  • Polysaccharides, Bacterial
  • RetS protein, Pseudomonas aeruginosa
  • cyclic GMP-binding protein
  • exopolysaccharide, Pseudomonas
  • Phosphorus-Oxygen Lyases
  • diguanylate cyclase