Helicobacter pylori adhesin HopQ disrupts trans dimerization in human CEACAM s

• DOI: 10.15252/embj.201798665
• Publication Date: 2018-06-01T10:00:35Z
• Authors: Kristof Moonens; Youssef Hamway; Matthias Neddermann; Marc Reschke; Nicole Tegtmeyer; Tobias Kruse; Robert Kammerer; Raquel Mejías‐Luque; Bernhard B Singer; Steffen Backert; Markus Gerhard; Han Remaut
• Keywords: 0301 basic medicine; Helicobacter pylori; HopQ; Medizin; CHO Cells; bacterial adhesion; 03 medical and health sciences; Cricetulus; Bacterial Proteins; Antigens, CD; Cell Line, Tumor; CagA delivery; Animals; Humans; Protein Multimerization; CEACAM1; Cell Adhesion Molecules

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.