title: Unraveling functional significance of natural variations of a human galectin by glycodendrimersomes with programmable glycan surface.
abstract: Surface-presented glycans (complex carbohydrates) are docking sites for adhesion/growth-regulatory galectins within cell-cell/matrix interactions. Alteration of the linker length in human galectin-8 and single-site mutation (F19Y) are used herein to illustrate the potential of glycodendrimersomes with programmable glycan displays as a model system to reveal the functional impact of natural sequence variations in trans recognition. Extension of the linker length slightly reduces lectin capacity as agglutinin and slows down aggregate formation at low ligand surface density. The mutant protein is considerably less active as agglutinin and less sensitive to low-level ligand presentation. The present results suggest that mimicking glycan complexity and microdomain occurrence on the glycodendrimersome surface can provide key insights into mechanisms to accomplish natural selectivity and specificity of lectins in structural and topological terms.
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323;
authors.forename: Shaodong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323;
authors.forename: Ralph-Olivier
authors.initials: RO
authors.lastname: Moussodia
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, 80539 Munich, Germany; and.
authors.forename: Sabine
authors.initials: S
authors.lastname: Vértesy
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, 80539 Munich, Germany; and.
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.affiliation: Institute of Computational Molecular Science, Temple University, Philadelphia, PA 19122 mlklein@temple.edu percec@sas.upenn.edu.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, 80539 Munich, Germany; and.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323; mlklein@temple.edu percec@sas.upenn.edu.
authors.forename: Virgil
authors.initials: V
authors.lastname: Percec
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000276:immunology; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D037161:Galectins / Q000737:chemistry*; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D037161:Galectins; C091991:LGALS8 protein, human; D037102:Lectins; D008024:Ligands; D011134:Polysaccharides
keywords: adhesion; agglutination; glycobiology; membrane mimic; self-assembly