Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides.
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.
Bouillaut
L
L
INRA, UR1249, F-78285 Guyancourt, France.
Perchat
S
S
Arold
S
S
Zorrilla
S
S
Slamti
L
L
Henry
C
C
Gohar
M
M
Declerck
N
N
Lereclus
D
D
D000595:Amino Acid Sequence; D001409:Bacillus cereus / Q000472:pathogenicity*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D053038:Quorum Sensing; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
D001426:Bacterial Proteins; D009842:Oligopeptides; C466079:PapR protein, Bacillus cereus; C099480:PlcR protein, Bacillus; D015534:Trans-Activators; D037521:Virulence Factors