6IAL

Porcine E.coli heat-labile enterotoxin B-pentamer in complex with Lacto-N-neohexaose

Summary for 6IAL

• Entry DOI: 10.2210/pdb6ial/pdb
• Related: 2XRQ 2XRS
• Descriptor: Heat-labile enterotoxin B chain, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-6)]beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, GLYCEROL, ... (6 entities in total)
• Functional Keywords: toxin, porcine, heat-labile enterotoxin, etec, e.coli, lectin, complex, x-ray crystal structure, carbohydrate, protein-carbohydrate interaction, ligand, lacto-n-neohexaose
• Biological source: Escherichia coli
• Total number of polymer chains: 10
• Total formula weight: 120767.44

Authors

Heim, J.B.,Heggelund, J.E.,Krengel, U. (deposition date: 2018-11-27, release date: 2019-02-27, Last modification date: 2024-11-13)

Primary citation

Heggelund, J.E.,Heim, J.B.,Bajc, G.,Hodnik, V.,Anderluh, G.,Krengel, U.
Specificity ofEscherichia coliHeat-Labile Enterotoxin Investigated by Single-Site Mutagenesis and Crystallography.
Int J Mol Sci, 20:-, 2019

PubMed Abstract: Diarrhea caused by enterotoxigenic (ETEC) is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to -acetyllactosamine-terminating glycosphingolipids. Here, we probed 11 single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 Å crystal structure of pLTB in complex with branched lacto--neohexaose (Galβ4GlcNAcβ6[Galβ4GlcNAcβ3]Galβ4Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity.

PubMed: 30736336
DOI: 10.3390/ijms20030703

Experimental method

X-RAY DIFFRACTION (1.45 Å)