Genetic and Structural Analyses of RRNPP Intercellular Peptide Signaling of Gram-Positive Bacteria

Annu Rev Genet. 2017 Nov 27;51:311-333. doi: 10.1146/annurev-genet-120116-023507. Epub 2017 Sep 6.


Bacteria use diffusible chemical messengers, termed pheromones, to coordinate gene expression and behavior among cells in a community by a process known as quorum sensing. Pheromones of many gram-positive bacteria, such as Bacillus and Streptococcus, are small, linear peptides secreted from cells and subsequently detected by sensory receptors such as those belonging to the large family of RRNPP proteins. These proteins are cytoplasmic pheromone receptors sharing a structurally similar pheromone-binding domain that functions allosterically to regulate receptor activity. X-ray crystal structures of prototypical RRNPP members have provided atomic-level insights into their mechanism and regulation by pheromones. This review provides an overview of RRNPP prototype signaling; describes the structure-function of this protein family, which is spread widely among gram-positive bacteria; and suggests approaches to target RRNPP systems in order to manipulate beneficial and harmful bacterial behaviors.

Keywords: Rap phosphatase; peptide pheromone; quorum sensing; repeat domain; signal transduction.

Publication types

  • Review

MeSH terms

  • Bacillus / classification
  • Bacillus / genetics*
  • Bacillus / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Biological Transport
  • Gene Expression Regulation, Bacterial*
  • Models, Molecular
  • Peptides / genetics
  • Peptides / metabolism
  • Pheromones / genetics*
  • Pheromones / metabolism
  • Phylogeny
  • Quorum Sensing / genetics
  • Receptors, Pheromone / genetics*
  • Receptors, Pheromone / metabolism
  • Signal Transduction
  • Streptococcus / classification
  • Streptococcus / genetics*
  • Streptococcus / metabolism
  • Structure-Activity Relationship
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Bacterial Proteins
  • Peptides
  • Pheromones
  • Receptors, Pheromone
  • Trans-Activators