title: Differential binding and activity of the pore-forming toxin sticholysin II in model membranes containing diverse ceramide-derived lipids.
abstract: Sticholysin II is a pore-forming toxin produced by the sea anemone Stichodactyla helianthus that belongs to the actinoporin protein family. The high affinity of actinoporins for sphingomyelin (SM)-containing membranes has been well documented. However, the molecular determinants that define this affinity have not been fully clarified. Here, we have examined the binding and permeabilizing activity of StII to different single and mixed lipidic systems by combining lipid monolayers, liposomes, and permeabilizing assays. This study characterizes the contribution of ceramide-derived compounds for StII-membrane interaction. Molecular dynamics simulations revealed a differential binding mode of StII with the polar head group of SM and PC. The electrostatic interaction energies were the major energetic contributors to the better affinity of StII for SM compared to PC, while the van der Waals interaction energies were the major driving forces of the better affinity of StII for SM respect to Cer. Furthermore, the presence of sugar residues in glycosphingolipids modulated binding and pore-formation by actinoporins probably by hindering StII to reach relevant structural motifs in membrane for binding or inducing a non-competent adsorption to membrane. Our results demonstrate that StII-membrane interaction, leading to pore formation, may critically respond to changes in lipid head group properties, and the access to SM interfacial structural motif.
authors.affiliation: Center for Protein Studies, Faculty of Biology, Havana University, Havana, CP 10400, Cuba.
authors.forename: Carmen
authors.initials: C
authors.lastname: Soto
authors.affiliation: Center for Protein Studies, Faculty of Biology, Havana University, Havana, CP 10400, Cuba.
authors.forename: Anaixis
authors.initials: A
authors.lastname: Del Valle
authors.affiliation: Center for Protein Studies, Faculty of Biology, Havana University, Havana, CP 10400, Cuba.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Valiente
authors.affiliation: Interfaculty Institute of Biochemistry, Tubingen University, Hoppeseyler Strasse 4, 72076, Tubingen, Germany.
authors.forename: Uris
authors.initials: U
authors.lastname: Ros
authors.affiliation: Center for Protein Studies, Faculty of Biology, Havana University, Havana, CP 10400, Cuba.
authors.forename: María E
authors.initials: ME
authors.lastname: Lanio
authors.affiliation: Center of Molecular Immunology, Havana, CP 11600, Cuba.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Hernández
authors.affiliation: Center for Protein Studies, Faculty of Biology, Havana University, Havana, CP 10400, Cuba. Electronic address: calvarez@fbio.uh.cu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D003064:Cnidarian Venoms / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D012615:Sea Anemones / Q000737:chemistry*; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D003064:Cnidarian Venoms; D008051:Lipid Bilayers; D008081:Liposomes; D013109:Sphingomyelins; C404794:sticholysin II
keywords: Actinoporin; Ceramide; Phosphorylcholine; Sphingomyelin; Sticholysin II