dc.date.accessioned | 2019-04-03T11:14:50Z | |
dc.date.available | 2019-04-03T11:14:50Z | |
dc.date.created | 2019-02-13T17:26:02Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Heggelund, Julie Elisabeth Heim, Joel Benjamin Bajc, Gregor Hodnik, Vesna Anderluh, Gregor Krengel, Ute . Specificity of Escherichia coli heat-Labile enterotoxin investigated by single-site mutagenesis and crystallography. International Journal of Molecular Sciences. 2019 | |
dc.identifier.uri | http://hdl.handle.net/10852/67510 | |
dc.description.abstract | Diarrhea caused by enterotoxigenic Escherichia coli (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 N-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-N-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. | en_US |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Specificity of Escherichia coli heat-Labile enterotoxin investigated by single-site mutagenesis and crystallography | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Heggelund, Julie Elisabeth | |
dc.creator.author | Heim, Joel Benjamin | |
dc.creator.author | Bajc, Gregor | |
dc.creator.author | Hodnik, Vesna | |
dc.creator.author | Anderluh, Gregor | |
dc.creator.author | Krengel, Ute | |
cristin.unitcode | 185,15,23,30 | |
cristin.unitname | Farmasøytisk biovitenskap | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1677187 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=International Journal of Molecular Sciences&rft.volume=&rft.spage=&rft.date=2019 | |
dc.identifier.jtitle | International Journal of Molecular Sciences | |
dc.identifier.doi | http://dx.doi.org/10.3390/ijms20030703 | |
dc.identifier.urn | URN:NBN:no-70696 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1422-0067 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/67510/2/ijms-20-00703.pdf | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/67510/3/ijms-20-00703_Supplement.pdf | |
dc.type.version | PublishedVersion | |