Structural insights into polymorphic ABO glycan binding by Helicobacter pylori

Moonens, Kristof, Gideonsson, Paer, Subedi, Suresh, Bugaytsova, Jeanna, Romao, Ema, Mendez, Melissa, Norden, Jenny, Fallah, Mahsa, Rakhimova, Lena, Shevtsova, Anna, Lahmann, Martina, Castaldo, Gaetano, Brannstrom, Kristoffer, Coppens, Fanny, Lo, Alvin W., Ny, Tor, Solnick, Jay V., Vandenbussche, Guy, Oscarson, Stefan, Hammarstrom, Lennart, Arnqvist, Anna, Berg, Douglas E., Muyldermans, Serge, Boren, Thomas and Remaut, Han (2016) Structural insights into polymorphic ABO glycan binding by Helicobacter pylori. Cell Host and Microbe, 19 1: 55-66. doi:10.1016/j.chom.2015.12.004

Author Moonens, Kristof
Gideonsson, Paer
Subedi, Suresh
Bugaytsova, Jeanna
Romao, Ema
Mendez, Melissa
Norden, Jenny
Fallah, Mahsa
Rakhimova, Lena
Shevtsova, Anna
Lahmann, Martina
Castaldo, Gaetano
Brannstrom, Kristoffer
Coppens, Fanny
Lo, Alvin W.
Ny, Tor
Solnick, Jay V.
Vandenbussche, Guy
Oscarson, Stefan
Hammarstrom, Lennart
Arnqvist, Anna
Berg, Douglas E.
Muyldermans, Serge
Boren, Thomas
Remaut, Han
Title Structural insights into polymorphic ABO glycan binding by Helicobacter pylori
Formatted title
Structural insights into polymorphic ABO glycan binding by Helicobacter pylori
Journal name Cell Host and Microbe   Check publisher's open access policy
ISSN 1934-6069
Publication date 2016-01-13
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.chom.2015.12.004
Open Access Status Not Open Access
Volume 19
Issue 1
Start page 55
End page 66
Total pages 12
Place of publication Cambridge, MA United States
Publisher Cell Press
Collection year 2017
Language eng
Formatted abstract
The Helicobacter pylori adhesin BabA binds mucosal ABO/Leb blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Leb binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Leb-expressing mice, providing perspectives on possible H. pylori eradication therapies.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 12 Apr 2016, 18:35:51 EST by Alvin Lo Wei Han on behalf of School of Chemistry & Molecular Biosciences