5JUF

Crystal structure of the apo form of ComR from S. thermophilus.

Summary for 5JUF

• Entry DOI: 10.2210/pdb5juf/pdb
• Descriptor: Transcriptional regulator, SULFATE ION (3 entities in total)
• Functional Keywords: rnpp, transcriptional activator, tpr, hth, apo, quorum-sensor, competence regulator, transcription
• Biological source: Streptococcus thermophilus LMD-9
• Total number of polymer chains: 1
• Total formula weight: 36932.25

Authors

Talagas, A.,Fontaine, L.,Ledesma, L.,Li de la Sierra-Gallay, I.,Hols, P.,Nessler, S. (deposition date: 2016-05-10, release date: 2016-10-26, Last modification date: 2025-10-01)

Primary citation

Talagas, A.,Fontaine, L.,Ledesma-Garca, L.,Mignolet, J.,Li de la Sierra-Gallay, I.,Lazar, N.,Aumont-Nicaise, M.,Federle, M.J.,Prehna, G.,Hols, P.,Nessler, S.
Structural Insights into Streptococcal Competence Regulation by the Cell-to-Cell Communication System ComRS.
PLoS Pathog., 12:e1005980-e1005980, 2016

PubMed Abstract: In Gram-positive bacteria, cell-to-cell communication mainly relies on extracellular signaling peptides, which elicit a response either indirectly, by triggering a two-component phosphorelay, or directly, by binding to cytoplasmic effectors. The latter comprise the RNPP family (Rgg and original regulators Rap, NprR, PrgX and PlcR), whose members regulate important bacterial processes such as sporulation, conjugation, and virulence. RNPP proteins are increasingly considered as interesting targets for the development of new antibacterial agents. These proteins are characterized by a TPR-type peptide-binding domain, and except for Rap proteins, also contain an N-terminal HTH-type DNA-binding domain and display a transcriptional activity. Here, we elucidate the structure-function relationship of the transcription factor ComR, a new member of the RNPP family, which positively controls competence for natural DNA transformation in streptococci. ComR is directly activated by the binding of its associated pheromone XIP, the mature form of the comX/sigX-inducing-peptide ComS. The crystal structure analysis of ComR from Streptococcus thermophilus combined with a mutational analysis and in vivo assays allows us to propose an original molecular mechanism of the ComR regulation mode. XIP-binding induces release of the sequestered HTH domain and ComR dimerization to allow DNA binding. Importantly, we bring evidence that this activation mechanism is conserved and specific to ComR orthologues, demonstrating that ComR is not an Rgg protein as initially proposed, but instead constitutes a new member of the RNPP family. In addition, identification of XIP and ComR residues important for competence activation constitutes a crucial step towards the design of antagonistic strategies to control gene exchanges among streptococci.

PubMed: 27907189
DOI: 10.1371/journal.ppat.1005980

Experimental method

X-RAY DIFFRACTION (1.946 Å)