5LP2

Adhesin domain of the type 1 HopQ of Helicobacter pylori strain G27

5LP2 の概要

• エントリーDOI: 10.2210/pdb5lp2/pdb
• 分子名称: HopQ (2 entities in total)
• 機能のキーワード: adhesin, helicobacter outer membrane protein, ectodomain, ceacam, cell adhesion
• 由来する生物種: Helicobacter pylori (strain G27)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 186520.72

構造登録者

Moonens, K.,Kruse, T.,Gerhard, M.,Remaut, H. (登録日: 2016-08-11, 公開日: 2016-10-12, 最終更新日: 2024-01-10)

主引用文献

Javaheri, A.,Kruse, T.,Moonens, K.,Mejias-Luque, R.,Debraekeleer, A.,Asche, C.I.,Tegtmeyer, N.,Kalali, B.,Bach, N.C.,Sieber, S.A.,Hill, D.J.,Koniger, V.,Hauck, C.R.,Moskalenko, R.,Haas, R.,Busch, D.H.,Klaile, E.,Slevogt, H.,Schmidt, A.,Backert, S.,Remaut, H.,Singer, B.B.,Gerhard, M.
Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs.
Nat Microbiol, 2:16189-16189, 2016

PubMed Abstract: Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a β-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.

PubMed: 27748768
DOI: 10.1038/nmicrobiol.2016.189

実験手法

X-RAY DIFFRACTION (2.6 Å)