|Title||adhesin HopQ disrupts dimerization in human CEACAMs.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Moonens, 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|
|Date Published||2018 Jul 02|
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.
|Alternate Journal||EMBO J.|
|PubMed Central ID||PMC6028033|
adhesin HopQ disrupts dimerization in human CEACAMs.