dc.date.accessioned | 2020-07-13T18:07:01Z | |
dc.date.available | 2020-07-13T18:07:01Z | |
dc.date.created | 2019-09-26T15:48:37Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Heim, Joel Benjamin Hodnik, Vesna Heggelund, Julie Elisabeth Anderluh, Gregor Krengel, Ute . Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site. Scientific Reports. 2019, 9 | |
dc.identifier.uri | http://hdl.handle.net/10852/77836 | |
dc.description.abstract | Cholera is a life-threatening diarrhoeal disease caused by the human pathogen Vibrio cholerae. Infection occurs after ingestion of the bacteria, which colonize the human small intestine and secrete their major virulence factor – the cholera toxin (CT). The GM1 ganglioside is considered the primary receptor of the CT, but recent studies suggest that also fucosylated receptors such as histo-blood group antigens are important for cellular uptake and toxicity. Recently, a special focus has been on the histo-blood group antigen Lewisx (Lex), however, where and how the CT binds to Lex remains unclear. Here we report the high-resolution crystal structure (1.5 Å) of the receptor-binding B-subunits of the CT bound to the Lex trisaccharide, and complementary quantitative binding data for CT holotoxins. Lex, and also L-fucose alone, bind to the secondary binding site of the toxin, distinct from the GM1 binding site. In contrast, fucosyl-GM1 mainly binds to the primary binding site due to high-affinity interactions of its GM1 core. Lex is the first histo-blood group antigen of non-secretor phenotype structurally investigated in complex with CT. Together with the quantitative binding data, this allows unique insight into why individuals with non-secretor phenotype are more prone to severe cholera than so-called ‘secretors’. | en_US |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Heim, Joel Benjamin | |
dc.creator.author | Hodnik, Vesna | |
dc.creator.author | Heggelund, Julie Elisabeth | |
dc.creator.author | Anderluh, Gregor | |
dc.creator.author | Krengel, Ute | |
cristin.unitcode | 185,15,12,0 | |
cristin.unitname | Kjemisk institutt | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1729758 | |
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=Scientific Reports&rft.volume=9&rft.spage=&rft.date=2019 | |
dc.identifier.jtitle | Scientific Reports | |
dc.identifier.volume | 9 | |
dc.identifier.issue | 1 | |
dc.identifier.doi | https://doi.org/10.1038/s41598-019-48579-2 | |
dc.identifier.urn | URN:NBN:no-80940 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2045-2322 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/77836/2/s41598-019-48579-2.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 12243 | |
dc.relation.project | NFR/247730 | |