Nucleic Acids Research Advance Access originally published online on May 20, 2008
Nucleic Acids Research 2008 36(11):3791-3801; doi:10.1093/nar/gkn149
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Nucleic Acids Research, 2008, Vol. 36, No. 11 3791-3801
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides
1INRA, UR1249, F-78285 Guyancourt, 2INSERM, Unité 554, Montpellier, France and Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, Montpellier and 3INRA, UR477, F-78350 Jouy-en-Josas, France
*To whom correspondence should be addressed. Tel: +33 (0)1 30 83 36 35; Fax: +33 (0)1 30 83 80 97; Email: Didier.Lereclus{at}jouy.inra.fr Correspondence may also be addressed to N. Declerck. Tel: +33 (0)4 67 41 79 11; Fax: +33 (0)4 67 41 79 13; Email: Nathalie.Declerck{at}cbs.cnrs.fr
Received February 14, 2008. Revised March 13, 2008. Accepted March 17, 2008.
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.
Present address: L. Slamti, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Channing laboratories, 181 Longwood Ave, 02115 Boston MA, USA