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Structural insights into polymorphic abo glycan binding by Helicobacter pylori
DOI:
10.1016/j.chom.2015.12.004
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
(Umeå University)
,
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.
Diamond Keywords: Bacteria
Subject Areas:
Biology and Bio-materials,
Medicine
Instruments:
I04-1-Macromolecular Crystallography (fixed wavelength)
,
I04-Macromolecular Crystallography
,
I24-Microfocus Macromolecular Crystallography
Other Facilities: Soleil
Added On:
19/02/2016 12:05
Discipline Tags:
Pathogens
Infectious Diseases
Health & Wellbeing
Structural biology
Drug Discovery
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)