Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides

L. Bouillaut, S. Perchat, S. Arold, S. Zorrilla, L. Slamti, C. Henry, M. Gohar, Nathalie Declerck, Didier Lereclus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

The transcriptional regulator PlcR and its cognate cell-cell signalling peptide PapR form a quorum-sensing system that controls the expression of extra-cellular virulence factors in various species of the Bacillus cereus group. PlcR and PapR alleles are clustered into four groups defining four pherotypes. However, the molecular basis for group specificity remains elusive, largely because the biologically relevant PapR form is not known. Here, we show that the in vivo active form of PapR is the C-terminal heptapeptide of the precursor, and not the pentapeptide, as previously suggested. Combining genetic complementation, anisotropy assays and structural analysis we provide a detailed functional and structural explanation for the group specificity of the PlcR-PapR quorum-sensing system. We further show that the C-terminal helix of the PlcR regulatory domain, specifically the 278 residue, in conjunction with the N-terminal residues of the PapR heptapeptide determines this system specificity. Variability in the specificity-encoding regions of plcR and papR genes suggests that selection and evolution of quorum-sensing systems play a major role in adaptation and ecology of Bacilli.

Original languageEnglish (US)
Pages (from-to)3791-3801
Number of pages11
JournalNUCLEIC ACIDS RESEARCH
Volume36
Issue number11
DOIs
StatePublished - Jun 2008
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank N. Daou, C. Nielsen-LeRoux and N. Ramarao for the critical reading of the manuscript and G. André-Leroux for helpful discussions. We also acknowledge S. Leppla for the gift of antibodies and A. Guillot for the mass spectrometry technical help, A. Chavanieu and J.-F. Guichou for the synthesis of PapR peptides. S.Z. is the recipient of a Marie-Curie European International Fellowship (MCEIF-CT-2004-007320). L.B. received a PhD grant from the Institut National de la Recherche Agronomique (MICA) and the région Ile de France. This work was supported by the Agence Nationale de la Recherche (PNRA 013-04). Funding to pay the Open Access publication charges for this article was provided by INRA.

ASJC Scopus subject areas

  • Genetics

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