adhesin HopQ disrupts dimerization in human CEACAMs.

Title adhesin HopQ disrupts dimerization in human CEACAMs.
Publication TypeJournal Article
Year of Publication2018
AuthorsMoonens, K., Y. Hamway, M. Neddermann, M. Reschke, N. Tegtmeyer, T. Kruse, R. Kammerer, R. Mejías-Luque, B. B. Singer, S. Backert, M. Gerhard, and H. Remaut
JournalEMBO J
Volume37
Issue13
Date Published2018 Jul 02
ISSN1460-2075
Abstract

The human gastric pathogen 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 specificity toward human CEACAM receptors. Both HopQ alleles target the β-strands G, F, and C of C1ND, which form the 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 a route to influence CEACAM-mediated cell adherence and signaling events.

DOI10.15252/embj.201798665
Alternate JournalEMBO J.
PubMed ID29858229
PubMed Central IDPMC6028033
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