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Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

DOI: 10.1016/j.chom.2015.12.004 DOI Help

Authors: Kristof Moonens (Vrije Universiteit Brussel) , Pär Gideonsson (Umeå University) , Suresh Subedi (Vrije Universiteit Brussel) , Jeanna Bugaytsova (Umeå University) , Ema Romaõ (Vrije Universiteit Brussel) , Melissa Mendez (Umeå University) , Jenny Nordén (Umeå University) , Mahsa Fallah (Umeå University) , Lena Rakhimova (Umeå University) , Anna Shevtsova (Umeå University) , Martina Lahmann (Bangor University) , Gaetano Castaldo (Vrije Universiteit Brussel) , Kristoffer Brännström (Umeå University) , Fanny Coppens (Vrije Universiteit Brussel) , Alvin W Lo (Vrije Universiteit Brussel) , Tor Ny , Jay v Solnick (University of California) , Guy Vandenbussche (Université Libre de Bruxelles) , Stefan Oscarson (University College Dublin) , Lennart Hammarström (Karolinska Institute at Karolinska University Hospital) , Anna Arnqvist (Umeå University) , Douglas e Berg (University of California) , Serge Muyldermans (Vrije Universiteit Brussel) , Thomas Borén (Umeå University) , Han Remaut (Vrije Universiteit Brussel)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Host & Microbe , VOL 19 , PAGES 55 - 66

State: Published (Approved)
Published: January 2016
Diamond Proposal Number(s): 9426

Abstract: The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) 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 Le(b) 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 Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

Subject Areas: Biology and Bio-materials

Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: Soleil