

Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.
SEEK ID: https://funginet.hki-jena.de/publications/84
PubMed ID: 27748768
Projects: A5
Publication type: Not specified
Journal: Nat Microbiol
Citation: Nat Microbiol. 2016 Oct 17;2:16189. doi: 10.1038/nmicrobiol.2016.189.
Date Published: 18th Oct 2016
Registered Mode: Not specified

Views: 2578
Created: 12th Sep 2017 at 09:01
Last updated: 17th Jan 2024 at 10:24

This item has not yet been tagged.

None