biostudies-literatureWilkening RVNIAID NIH HHSBurroughs Wellcome FundNational Institutes of Health20544-20557https://www.ebi.ac.uk/biostudies/studies/S-EPMC5733591biostudies-literatureUnknown292(50)Rap/Rgg/NprR/PlcR/PrgX (RRNPP) quorum-sensing systems use extracellular peptide pheromones that are detected by cytoplasmic receptors to regulate gene expression in firmicute bacteria. Rgg-type receptors are allosterically regulated through direct pheromone binding to control transcriptional activity; however, the receptor activation mechanism remains poorly understood. Previous work has identified a disulfide bond between Cys-45 residues within the homodimer interface of Rgg2 from <i>Streptococcus dysgalactiae</i> (Rgg2_Sd). Here, we compared two Rgg2_Sd(C45S) X-ray crystal structures with that of wild-type Rgg2_Sd and found that in the absence of the intermolecular disulfide, the Rgg2_Sd dimer interface is destabilized and Rgg2_Sd can adoThe Journal of biological chemistryActivating mutations in quorum-sensing regulator Rgg2 and its conformational flexibility in the absence of an intermolecular disulfide bond.PMC5733591R01 AI091779R01 AI125452AI125452AI091779Neiditch MBCapodagli GCTylor KMFederle MJKhataokar AWilkening RVfalseActivating mutations in quorum-sensing regulator Rgg2 and its conformational flexibility in the absence of an intermolecular disulfide bond.Rap/Rgg/NprR/PlcR/PrgX (RRNPP) quorum-sensing systems use extracellular peptide pheromones that are detected by cytoplasmic receptors to regulate gene expression in firmicute bacteria. Rgg-type receptors are allosterically regulated through direct pheromone binding to control transcriptional activity; however, the receptor activation mechanism remains poorly understood. Previous work has identified a disulfide bond between Cys-45 residues within the homodimer interface of Rgg2 from <i>Streptococcus dysgalactiae</i> (Rgg2_Sd). Here, we compared two Rgg2_Sd(C45S) X-ray crystal structures with that of wild-type Rgg2_Sd and found that in the absence of the intermolecular disulfide, the Rgg2_Sd dimer interface is destabilized and Rgg2_Sd can ado2017-01-01T00:00:00Z2017 Dec2026-05-02T09:17:50.535Z2019-03-27T00:11:22ZS-EPMC57335912903042910.1074/jbc.m117.80167010.1074/jbc.M117.801670