6hmy
Cholera toxin classical B-pentamer in complex with fucosyl-GM1
Structural highlights
FunctionCHTB_VIBCH The B subunit pentameric ring directs the A subunit to its target by binding to the GM1 gangliosides present on the surface of the intestinal epithelial cells. It can bind five GM1 gangliosides. It has no toxic activity by itself. Publication Abstract from PubMedCholera 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. See AlsoReferences
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