Helicobacter pylori adhesin HopQ disrupts trans dimerization in human CEACAMs

EMBO J. 2018 Jul 2;37(13):e98665. doi: 10.15252/embj.201798665. Epub 2018 Jun 1.


The human gastric pathogen Helicobacter pylori is a major causative agent of gastritis, peptic ulcer disease, and gastric cancer. As part of its adhesive lifestyle, the bacterium targets members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family by the conserved outer membrane adhesin HopQ. The HopQ-CEACAM1 interaction is associated with inflammatory responses and enables the intracellular delivery and phosphorylation of the CagA oncoprotein via a yet unknown mechanism. Here, we generated crystal structures of HopQ isotypes I and II bound to the N-terminal domain of human CEACAM1 (C1ND) and elucidated the structural basis of H. pylori specificity toward human CEACAM receptors. Both HopQ alleles target the β-strands G, F, and C of C1ND, which form the trans dimerization interface in homo- and heterophilic CEACAM interactions. Using SAXS, we show that the HopQ ectodomain is sufficient to induce C1ND monomerization and thus providing H. pylori a route to influence CEACAM-mediated cell adherence and signaling events.

Keywords: Helicobacter pylori; CEACAM1; CagA delivery; HopQ; bacterial adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / physiology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / physiology*
  • CHO Cells
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / physiology*
  • Cell Line, Tumor
  • Cricetulus
  • Helicobacter pylori / physiology*
  • Humans
  • Protein Multimerization


  • Antigens, CD
  • Bacterial Proteins
  • Cell Adhesion Molecules