|Title||Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Moonens, K., P. Gideonsson, S. Subedi, J. Bugaytsova, E. Romão, M. Mendez, J. Nordén, M. Fallah, L. Rakhimova, A. Shevtsova, M. Lahmann, G. Castaldo, K. Brännström, F. Coppens, A. W. Lo, T. Ny, J. V. Solnick, G. Vandenbussche, S. Oscarson, L. Hammarström, A. Arnqvist, D. E. Berg, S. Muyldermans, T. Borén, and H. Remaut|
|Journal||Cell Host Microbe|
|Date Published||2016 Jan 13|
|Keywords||ABO Blood-Group System, Adhesins, Bacterial, Animals, Binding Sites, Helicobacter Infections, Helicobacter pylori, Humans, Mice, Models, Molecular, Polysaccharides, Protein Binding|
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.
|Alternate Journal||Cell Host Microbe|
|PubMed Central ID||PMC4793151|
|Grant List||R01 AI070803 / AI / NIAID NIH HHS / United States |
R01 AI081037 / AI / NIAID NIH HHS / United States
Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori.