5CHH

Crystal structure of transcriptional regulator CdpR from Pseudomonas aeruginosa

Summary for 5CHH

• Entry DOI: 10.2210/pdb5chh/pdb
• Descriptor: AraC family transcriptional regulator (2 entities in total)
• Functional Keywords: quorum-sensing, atp-dependent protease, protein degradation, bacterial virulence, transcription
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 39231.79

Authors

Zhao, J.R.,Yu, X.,Zhu, M.,Kang, H.P.,Kong, W.N.,Ma, J.B.,Deng, X.,Gan, J.H.,Liang, H.H. (deposition date: 2015-07-10, release date: 2016-05-18, Last modification date: 2024-10-23)

Primary citation

Zhao, J.R.,Yu, X.,Zhu, M.,Kang, H.P.,Ma, J.B.,Wu, M.,Gan, J.H.,Deng, X.,Liang, H.H.
Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa
Plos Biol., 14:e1002449-e1002449, 2016

PubMed Abstract: Although quorum-sensing (QS) systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS). Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR), and its C-terminal HTH (helix-turn-helix) domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator). Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.

PubMed: 27119725
DOI: 10.1371/journal.pbio.1002449

Experimental method

X-RAY DIFFRACTION (1.85 Å)