Helicobacter pylori adhesin HopQ disrupts trans dimerization in human CEACAMs

Abstract

<p id="d8768826e449">The human gastric pathogen <i>Helicobacter pylori</i> 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 ( <span style="fixed-case">CEACAM</span>) family by the conserved outer membrane adhesin HopQ. The HopQ– <span style="fixed-case">CEACAM</span>1 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 <span style="fixed-case">II</span> bound to the N‐terminal domain of human <span style="fixed-case">CEACAM</span>1 (C1 <span style="fixed-case">ND</span>) and elucidated the structural basis of <i>H. pylori</i> specificity toward human <span style="fixed-case">CEACAM</span> receptors. Both HopQ alleles target the β‐strands G, F, and C of C1 <span style="fixed-case">ND</span>, which form the <i>trans</i> dimerization interface in homo‐ and heterophilic <span style="fixed-case">CEACAM</span> interactions. Using <span style="fixed-case">SAXS</span>, we show that the HopQ ectodomain is sufficient to induce C1 <span style="fixed-case">ND</span> monomerization and thus providing <i>H. pylori</i> a route to influence <span style="fixed-case">CEACAM</span>‐mediated cell adherence and signaling events. </p>