title: Introduction of selectin-like binding specificity into a homologous mannose-binding protein.
abstract: The structures of the ligand-binding C-type carbohydrate-recognition domains of selectin cell adhesion molecules and of mannose-binding proteins (MBPs) are similar to each other even though these proteins bind very different carbohydrate ligands. Our current understanding of ligand binding by E-selectin is based on structural studies of unliganded E-selectin and of MBP-carbohydrate complexes, combined with results from mutagenesis of E-selectin. Five regions of E-selectin that differ in sequence from the corresponding regions of MBP have been introduced into the carbohydrate-recognition domain of MBP. Four of the changes have little effect on ligand binding. Insertion of one stretch of positively charged amino acids alters the sugar binding selectivity of the domain so that it now binds HL-60 cells and serum albumin derivatized with sialyl-Lewis X tetrasaccharide, thus mimicking the properties of E-selectin.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York 10032, USA.
authors.forename: O
authors.initials: O
authors.lastname: Blanck
authors.forename: S T
authors.initials: ST
authors.lastname: Iobst
authors.forename: C
authors.initials: C
authors.lastname: Gabel
authors.forename: K
authors.initials: K
authors.lastname: Drickamer
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D037241:Mannose-Binding Lectins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D009844:Oligosaccharides / Q000378:metabolism; D019087:Selectins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; D037241:Mannose-Binding Lectins; D009838:Oligodeoxyribonucleotides; D009844:Oligosaccharides; D019087:Selectins; C058981:sialyl-Le(a) oligosaccharide; D002118:Calcium