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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 55-66 |
| Number of pages | 12 |
| Journal | Cell Host and Microbe |
| Volume | 19 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 13 2016 |
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ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Cancer Research
- Molecular Biology
Cite this
Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori. / Moonens, Kristof; Gideonsson, Pär; Subedi, Suresh; Bugaytsova, Jeanna; Romaõ, Ema; Mendez, Melissa; Nordén, Jenny; Fallah, Mahsa; Rakhimova, Lena; Shevtsova, Anna; Lahmann, Martina; Castaldo, Gaetano; Brännström, Kristoffer; Coppens, Fanny; Lo, Alvin W.; Ny, Tor; Solnick, Jay V; Vandenbussche, Guy; Oscarson, Stefan; Hammarström, Lennart; Arnqvist, Anna; Berg, Douglas E.; Muyldermans, Serge; Borén, Thomas; Remaut, Han.
In: Cell Host and Microbe, Vol. 19, No. 1, 13.01.2016, p. 55-66.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori
AU - Moonens, Kristof
AU - Gideonsson, Pär
AU - Subedi, Suresh
AU - Bugaytsova, Jeanna
AU - Romaõ, Ema
AU - Mendez, Melissa
AU - Nordén, Jenny
AU - Fallah, Mahsa
AU - Rakhimova, Lena
AU - Shevtsova, Anna
AU - Lahmann, Martina
AU - Castaldo, Gaetano
AU - Brännström, Kristoffer
AU - Coppens, Fanny
AU - Lo, Alvin W.
AU - Ny, Tor
AU - Solnick, Jay V
AU - Vandenbussche, Guy
AU - Oscarson, Stefan
AU - Hammarström, Lennart
AU - Arnqvist, Anna
AU - Berg, Douglas E.
AU - Muyldermans, Serge
AU - Borén, Thomas
AU - Remaut, Han
PY - 2016/1/13
Y1 - 2016/1/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959550066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959550066&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.12.004
DO - 10.1016/j.chom.2015.12.004
M3 - Article
C2 - 26764597
AN - SCOPUS:84959550066
VL - 19
SP - 55
EP - 66
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 1
ER -