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Helicobacter pylori adhesin HopQ disrupts trans dimerization in human CEACAMs

DOI: 10.15252/embj.201798665 DOI Help

Authors: Kristof Moonens (VIB, Brussels) , Youssef Hamway (Technische Universität München) , Matthias Neddermann (Friedrich Alexander University Erlangen) , Marc Reschke (University of Duisburg-Essen) , Nicole Tegtmeyer (Friedrich Alexander University Erlangen) , Tobias Kruse (Imevax GmbH) , Robert Kammerer (Friedrich-Loeffler Institut) , Raquel Mejías‐luque (Technische Universität; German Center for Infection Research) , Bernhard B Singer (University of Duisburg-Essen) , Steffen Backert (Friedrich Alexander University Erlangen) , Markus Gerhard (Technische Universität München; German Center for Infection Research) , Han Remaut (VIB, Brussels; Vrije Universiteit Brussel)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal

State: Published (Approved)
Published: June 2018
Diamond Proposal Number(s): 12718

Abstract: 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.

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

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography

Other Facilities: SOLEIL