title: 2-Hydroxy Fatty Acid Enantiomers of Gb3 Impact Shiga Toxin Binding and Membrane Organization.
abstract: Shiga toxin subunit B (STxB) binding to its cellular receptor Gb3 leads to the formation of protein-lipid clusters and bending of the membrane. A newly developed synthetic route allowed synthesizing the biologically most relevant Gb3-C24:1 2OH species with both, the natural (Gb3-R) as well as the unnatural (Gb3-S) configuration of the 2OH group. The derivatives bind STxB with identical nanomolar affinity, while the propensity to induce membrane tubules in giant unilamellar vesicles is more pronounced for Gb3-S. Fluorescence and atomic force microscopy images of phase-separated supported membranes revealed differences in the lateral organization of the protein on the membrane. Gb3-R favorably induces large and tightly packed protein clusters, while a lower protein density is found on Gb3-S doped membranes.
authors.affiliation: Institute of Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany.
authors.forename: Ole M
authors.initials: OM
authors.lastname: Schütte
authors.affiliation: Institute of Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany; Institute of Organic Chemistry, Technical University Braunschweig, Braunschweig, Germany.
authors.forename: Lukas J
authors.initials: LJ
authors.lastname: Patalag
authors.affiliation: Institute of Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany.
authors.forename: Lucas M C
authors.initials: LM
authors.lastname: Weber
authors.affiliation: Institute of Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Ries
authors.affiliation: Faculty of Biology and BIOSS-Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Römer
authors.affiliation: Institute of Organic Chemistry, Technical University Braunschweig, Braunschweig, Germany.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Werz
authors.affiliation: Institute of Organic and Biomolecular Chemistry, University of Göttingen, Göttingen, Germany. Electronic address: csteine@gwdg.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Steinem
mesh_terms: D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D006880:Hydroxy Acids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D022641:Shiga Toxin 2 / Q000737:chemistry / Q000378:metabolism*; D014281:Trihexosylceramides / Q000737:chemistry / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D006880:Hydroxy Acids; D022641:Shiga Toxin 2; D014281:Trihexosylceramides; D053835:Unilamellar Liposomes; C450841:shiga toxin 2 B subunit; C018549:globotriaosylceramide