4FSC

Crystal Structure of Bacillus thuringiensis PlcR in its apo form

Summary for 4FSC

• Entry DOI: 10.2210/pdb4fsc/pdb
• Related: 3U3W
• Descriptor: Transcriptional activator PlcR protein (1 entity in total)
• Functional Keywords: plcr apoform, hth dna-binding domain, quorum sensing, hth_3 (helix-turn-helix) domain, tpr_1 (tetratricopeptide repeats), pleiotropic regulator, transcriptional activator, transcription activator
• Biological source: Bacillus thuringiensis
• Total number of polymer chains: 4
• Total formula weight: 140245.14

Authors

Grenha, R.,Slamti, L.,Bouillaut, L.,Lereclus, D.,Nessler, S. (deposition date: 2012-06-27, release date: 2013-03-13, Last modification date: 2023-09-13)

Primary citation

Grenha, R.,Slamti, L.,Nicaise, M.,Refes, Y.,Lereclus, D.,Nessler, S.
Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR.
Proc.Natl.Acad.Sci.USA, 110:1047-1052, 2013

PubMed Abstract: 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.

PubMed: 23277548
DOI: 10.1073/pnas.1213770110

Experimental method

X-RAY DIFFRACTION (3.65 Å)