Fucosylation and protein glycosylation create functional receptors for cholera toxin.

Autor: Wands AM; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Fujita A; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., McCombs JE; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Cervin J; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Dedic B; Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Rodriguez AC; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Nischan N; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Bond MR; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Mettlen M; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Trudgian DC; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Lemoff A; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Quiding-Järbrink M; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Gustavsson B; Department of Surgery, University of Gothenburg, Gothenburg, Sweden., Steentoft C; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.; School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Clausen H; Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.; School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Mirzaei H; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States., Teneberg S; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.; Department of Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Yrlid U; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.; Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden., Kohler JJ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.
Jazyk: angličtina
Zdroj: ELife [Elife] 2015 Oct 29; Vol. 4, pp. e09545. Date of Electronic Publication: 2015 Oct 29.
DOI: 10.7554/eLife.09545
Abstrakt: Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we report that CTB binds cell surface glycoproteins. Relative contributions of gangliosides and glycoproteins to CTB binding depend on cell type, and CTB binds primarily to glycoproteins in colonic epithelial cell lines. Using a metabolically incorporated photocrosslinking sugar, we identified one CTB-binding glycoprotein and demonstrated that the glycan portion of the molecule, not the protein, provides the CTB interaction motif. We further show that fucosylated structures promote CTB entry into a colonic epithelial cell line and subsequent host cell intoxication. CTB-binding fucosylated glycoproteins are present in normal human intestinal epithelia and could play a role in cholera.
Databáze: MEDLINE