Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori

Moonens, K. and Gideonsson, P. and Subedi, S. and Bugaytsova, J. and Romaõ, E. and Mendez, M. and Nordén, J. and Fallah, M. and Rakhimova, L. and Shevtsova, A. and Lahmann, M. and Castaldo, G. and Brännström, K. and Coppens, F. and Lo, A.W. and Ny, T. and Solnick, J.V. and Vandenbussche, G. and Oscarson, S. and Hammarström, L. and Arnqvist, A. and Berg, D.E. and Muyldermans, S. and Borén, T. and Remaut, H. (2016) Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. Cell Host & Microbe, 19 (1). pp. 55-66. DOI: 10.1016/j.chom.2015.12.004

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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 redoxactive pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Leb-expressing mice, providing perspectives on possible H. pylori eradication therapies.

Item Type: Article
Subjects: Research Publications
Departments: College of Physical and Applied Sciences > School of Chemistry
Date Deposited: 20 Jan 2016 03:14
Last Modified: 12 Mar 2016 03:13
ISSN: 1931-3128
URI: http://e.bangor.ac.uk/id/eprint/6097
Identification Number: DOI: 10.1016/j.chom.2015.12.004
Publisher: Elsevier Press
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