Blood group antigen recognition by Escherichia coli heat-labile enterotoxin
Journal article, 2007

In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 angstrom crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAc alpha 3(Fuc alpha-2)Gal beta 4(Fuc alpha-3)Glc beta provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.

protein-carbohydrate interactions

EPITHELIAL-CELLS

GROUP SYSTEM

BINDING

PIG INTESTINAL-MUCOSA

clinical/epidemiological

CRYSTAL-STRUCTURE

data

DIFFRACTION DATA

GROUP-A

bacterial toxins

blood-group recognition

PROTEIN-STRUCTURE

SURFACE-PLASMON RESONANCE

CHOLERA-TOXIN

VIBRIO-CHOLERAE

X-ray crystal structure

Author

Åsa Holmner

Chalmers, Chemical and Biological Engineering

G. Askarieh

University of Oslo

M. Ökvist

University of Oslo

Ute Krengel

Chalmers, Chemical and Biological Engineering, Molecular Biotechnology

Journal of Molecular Biology

0022-2836 (ISSN)

Vol. 371 3 754-764

Subject Categories

Chemical Engineering

DOI

10.1016/j.jmb.2007.05.064

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