6W1A

Crystal structure of Streptococcus dysgalactiae SHP pheromone receptor Rgg2 bound to DNA

Summary for 6W1A

• Entry DOI: 10.2210/pdb6w1a/pdb
• Related: 4YV6
• Descriptor: Transcriptional regulator, DNA (30-MER), PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: pheromone binding, quorum sensing, dna binding protein, rrnpp, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Streptococcus dysgalactiae; More
• Total number of polymer chains: 4
• Total formula weight: 85995.15

Authors

Capodagli, G.C.,Neiditch, M.B. (deposition date: 2020-03-03, release date: 2020-10-21, Last modification date: 2024-11-06)

Primary citation

Capodagli, G.C.,Tylor, K.M.,Kaelber, J.T.,Petrou, V.I.,Federle, M.J.,Neiditch, M.B.
Structure-function studies of Rgg binding to pheromones and target promoters reveal a model of transcription factor interplay.
Proc.Natl.Acad.Sci.USA, 117:24494-24502, 2020

PubMed Abstract: Regulator gene of glucosyltransferase (Rgg) family proteins, such as Rgg2 and Rgg3, have emerged as primary quorum-sensing regulated transcription factors in species, controlling virulence, antimicrobial resistance, and biofilm formation. Rgg2 and Rgg3 function is regulated by their interaction with oligopeptide quorum-sensing signals called short hydrophobic peptides (SHPs). The molecular basis of Rgg-SHP and Rgg-target DNA promoter specificity was unknown. To close this gap, we determined the cryoelectron microscopy (cryo-EM) structure of Rgg3 bound to its quorum-sensing signal, SHP3, and the X-ray crystal structure of Rgg3 alone. Comparison of these structures with that of an Rgg in complex with cyclosporin A (CsA), an inhibitor of SHP-induced Rgg activity, reveals the molecular basis of CsA function. Furthermore, to determine how Rgg proteins recognize DNA promoters, we determined X-ray crystal structures of both Rgg2 and Rgg3 in complex with their target DNA promoters. The physiological importance of observed Rgg-DNA interactions was dissected using in vivo genetic experiments and in vitro biochemical assays. Based on these structure-function studies, we present a revised unifying model of Rgg regulatory interplay. In contrast to existing models, where Rgg2 proteins are transcriptional activators and Rgg3 proteins are transcriptional repressors, we propose that both are capable of transcriptional activation. However, when Rgg proteins with different activation requirements compete for the same DNA promoters, those with more stringent activation requirements function as repressors by blocking promoter access of SHP-bound conformationally active Rgg proteins. While a similar gene expression regulatory scenario has not been previously described, in all likelihood it is not unique to streptococci.

PubMed: 32907945
DOI: 10.1073/pnas.2008427117

Experimental method

X-RAY DIFFRACTION (2.8 Å)