Structural highlights
6hjd is a 10 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Ligands: | , , , , , |
Related: | 5elb, 5eld |
Gene: | ctxB ("Bacillo virgola del Koch" Trevisan 1884) |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
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 Lewis(x) (Le(x)), however, where and how the CT binds to Le(x) remains unclear. Here we report the high-resolution crystal structure (1.5 A) of the receptor-binding B-subunits of the CT bound to the Le(x) trisaccharide, and complementary quantitative binding data for CT holotoxins. Le(x), 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. Le(x) 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'.
Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site.,Heim JB, Hodnik V, Heggelund JE, Anderluh G, Krengel U Sci Rep. 2019 Aug 22;9(1):12243. doi: 10.1038/s41598-019-48579-2. PMID:31439922[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Heim JB, Hodnik V, Heggelund JE, Anderluh G, Krengel U. Crystal structures of cholera toxin in complex with fucosylated receptors point to importance of secondary binding site. Sci Rep. 2019 Aug 22;9(1):12243. doi: 10.1038/s41598-019-48579-2. PMID:31439922 doi:http://dx.doi.org/10.1038/s41598-019-48579-2