Structure of PlcR: Insights into virulence regulation and evolution of quorum sensing in Gram-positive bacteria

Declerck, Nathalie; Bouillaut, Laurent; Chaix, Denis; Rugani, Nathalie; Slamti, Leyla; Hoh, François; Lereclus, Didier; Arold, Stefan T.

doi:10.1073/pnas.0704501104

Cited by 140 publications

(253 citation statements)

References 43 publications

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“…The iCF10 inhibitory peptide binds in the same pocket of the TPR domain as cCF10, but it does not promote the activating conformational change (17,23). As described previously (8), PlcR and PrgX share a similar binding mode, although the effect of peptide binding is quite different.…”

Section: Discussionmentioning

confidence: 68%

“…These proteins share structural similarities: tetratricopeptide repeats (TPRs) forming a peptide binding domain (6) and a helix-turn-helix (HTH) DNA-binding domain (7) in the case of transcriptional regulators. They have been grouped in a new family of quorum sensors called RNPP, for Rap, NprR, PrgX, and PlcR (8).…”

mentioning

confidence: 99%

“…However, the structural basis for this specificity remains unknown. The crystal structure of the 34 kDa PlcR protein from group I in complex with the pentapeptide PapR5 (LPFEF) was published in 2007 (8). This binary complex is a dimer similar to the structure of the other RNPP transcriptional regulator PrgX (17).…”

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confidence: 99%

“…The first helix of the TPR domain comprises an N-terminal extension forming a long helix of 30 residues spanning over 40 Å, which connects the HTH-and TPR-domains. It has been named the linker helix (8). Finally, an additional helix, designated as capping helix (8), is found at the C terminus of the protein (Fig.…”

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confidence: 99%

“…It has been named the linker helix (8). Finally, an additional helix, designated as capping helix (8), is found at the C terminus of the protein (Fig. S1).…”

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confidence: 99%

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Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Grenha

Slamti

Nicaise

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The quorum-sensing regulator PlcR is the master regulator of most known virulence factors in Bacillus cereus. It is a helix-turn-helix (HTH)-type transcription factor activated upon binding of its cognate signaling peptide PapR on a tetratricopeptide repeat-type regulatory domain. The structural and functional properties of PlcR have defined a new family of sensor regulators, called the RNPP family (for Rap, NprR, PrgX, and PlcR), in Gram-positive bacteria. To fully understand the activation mechanism of PlcR, we took a closer look at the conformation changes induced upon binding of PapR and of its target DNA, known as PlcR-box. For that purpose we have determined the structures of the apoform of PlcR (Apo PlcR) and of the ternary complex of PlcR with PapR and the PlcR-box from the plcA promoter. Comparison of the apoform of PlcR with the previously published structure of the PlcR-PapR binary complex shows how a small conformational change induced in the C-terminal region of the tetratricopeptide repeat (TPR) domain upon peptide binding propagates via the linker helix to the N-terminal HTH DNA-binding domain. Further comparison with the PlcR-PapR-DNA ternary complex shows how the activation of the PlcR dimer allows the linker helix to undergo a drastic conformational change and subsequent proper positioning of the HTH domains in the major groove of the two half sites of the pseudopalindromic PlcR-box. Together with random mutagenesis experiments and interaction measurements using peptides from distinct pherogroups, this structural analysis allows us to propose a molecular mechanism for this functional switch

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Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…It has been named the linker helix (8). Finally, an additional helix, designated as capping helix (8), is found at the C terminus of the protein (Fig. S1).…”

mentioning

confidence: 99%

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Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Grenha

Slamti

Nicaise

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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New insights into the interaction between the quorum‐sensing receptor NprR and its DNA target, or the response regulator Spo0F

et al. 2016

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The NprR protein and NprRB signaling peptide comprise a bifunctional quorum–sensing system from the Bacillus cereus group that is involved in transcriptional activation through DNA‐binding and in sporulation initiation by binding to Spo0F. We characterized in vitro the direct interactions established by NprR that may be relevant for performing its two functions. Apo‐NprR interacted with Spo0F, but not with the target DNA. The NprRB signaling peptide SSKPDIVG that binds strongly to Apo‐NprR, failed to bind and disrupt the NprR‐Spo0F complex. Finally, the NprR‐NprRB complex bound both to Spo0F and the target DNA with similar affinity. Based on our findings, we propose that rather than a switch triggered by NprRB, the NprR/NprRB ratio and the availability of Spo0F binding sites define the function of NprR.

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Quorum Sensing in Bacillus Cereus in Relation to cysteine Metabolism and the Oxidative Stress response

Huillet

Gohar

2016

Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria

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A number of peptide-mediated quorum sensing (QS) systems regulate important biological functions in bacteria of the Bacillus cereus group. Sporulation, virulence and biofilm formation are controlled by such systems in these bacteria. PapR, a secreted heptapeptide, activates PlcR, the main transcriptional regulator of virulence in B. thuringiensis and B. cereus. We recently found that PlcRa, a PlcR paralogue, also works in QS and is involved in oxidative stress response and cysteine metabolism during the early stationary phase of bacterial growth. Notably, we have reported that PlcRa activates the expression of several genes involved in the pathway of cysteine synthesis from methionine including the S-adenosylmethionine (SAM) recycling pathway. This transcriptional control of SAM recycling pathway by PlcRa impacts another QS, the autoinducer-2 (AI-2) system. AI-2 is a signal metabolic molecule produced by LuxS, a central metabolic enzyme involved in SAM recycling, found in many bacterial species and thus proposed to enable interspecies communication. We have reported that B. cereus synthetizes and recognizes AI-2 as an extracellular signal. Most particularly, we have shown that AI-2 inhibits biofilm formation in a concentration-dependent manner.In this review, we provide an overview of these two QS systems in B.cereus species (signal production, detection, transduction) with the description of AI-2 connection. We highlight how CymR regulon -involved in the global regulation of gene expression in response to cysteine availability-together with PlcRa system is important for AI-2 production and present the role of PlcRa in oxidative stress response.

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Structure of PlcR: Insights into virulence regulation and evolution of quorum sensing in Gram-positive bacteria

Cited by 140 publications

References 43 publications

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR

New insights into the interaction between the quorum‐sensing receptor NprR and its DNA target, or the response regulator Spo0F

Quorum Sensing in Bacillus Cereus in Relation to cysteine Metabolism and the Oxidative Stress response

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