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PLoS One. 2013 Jun 6;8(6):e66202. doi: 10.1371/journal.pone.0066202. Print 2013.

Characterization of putative cholesterol recognition/interaction amino acid consensus-like motif of Campylobacter jejuni cytolethal distending toxin C.

Author information

  • 1Department of Microbiology, School of Medicine, Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. chl@mail.cmu.edu.tw

Abstract

Cytolethal distending toxin (CDT) produced by Campylobacter jejuni comprises a heterotrimeric complex formed by CdtA, CdtB, and CdtC. Among these toxin subunits, CdtA and CdtC function as essential proteins that mediate toxin binding to cytoplasmic membranes followed by delivery of CdtB into the nucleus. The binding of CdtA/CdtC to the cell surface is mediated by cholesterol, a major component in lipid rafts. Although the putative cholesterol recognition/interaction amino acid consensus (CRAC) domain of CDT has been reported from several bacterial pathogens, the protein regions contributing to CDT binding to cholesterol in C. jejuni remain unclear. Here, we selected a potential CRAC-like region present in the CdtC from C. jejuni for analysis. Molecular modeling showed that the predicted functional domain had the shape of a hydrophobic groove, facilitating cholesterol localization to this domain. Mutation of a tyrosine residue in the CRAC-like region decreased direct binding of CdtC to cholesterol rather than toxin intermolecular interactions and led to impaired CDT intoxication. These results provide a molecular link between C. jejuni CdtC and membrane-lipid rafts through the CRAC-like region, which contributes to toxin recognition and interaction with cholesterol.

PMID:
23762481
[PubMed - indexed for MEDLINE]
PMCID:
PMC3675143
Free PMC Article

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