title: Binding specificities of the sialoadhesin family of I-type lectins. Sialic acid linkage and substructure requirements for binding of myelin-associated glycoprotein, Schwann cell myelin protein, and sialoadhesin.
abstract: The carbohydrate binding specificities of three sialoadhesins, a subgroup of I-type lectins (immunoglobulin superfamily lectins), were compared by measuring lectin-transfected COS cell adhesion to natural and synthetic gangliosides. The neural sialoadhesins, myelin-associated glycoprotein (MAG) and Schwann cell myelin protein (SMP), had similar and stringent binding specificities. Each required an alpha2,3-linked sialic acid on the terminal galactose of a neutral saccharide core, and they shared the following rank-order potency of binding: GQ1balpha >> GD1a = GT1b >> GM3 = GM4 >> GM1, GD1b, GD3, GQ1b (nonbinders). In contrast, sialoadhesin had less exacting specificity, binding to gangliosides that bear either terminal alpha2,3- or alpha2,8-linked sialic acids with the following rank-order potency of binding: GQ1balpha > GD1a = GD1b = GT1b = GM3 = GM4 > GD3 = GQ1b >> GM1 (nonbinder). CD22 did not bind to any ganglioside tested. Binding of MAG, SMP, and sialoadhesin was abrogated by chemical modification of either the sialic acid carboxylic acid group or glycerol side chain on a target ganglioside. Synthetic ganglioside GM3 derivatives further distinguished lectin binding specificities. Deoxy and/or methoxy derivatives of the 4-, 7-, 8-, or 9-position of sialic acid attenuated or eliminated binding of MAG, as did replacement of the sialic acid acetamido group with a hydroxyl. In contrast, the 4- and 7-deoxysialic acid derivatives supported sialoadhesin binding at near control levels (the other derivatives did not support binding). These data are consistent with sialoadhesin binding to one face of the sialic acid moiety, whereas MAG (and SMP) may have more complex binding sites or may bind sialic acids only in the context of more restricted oligosaccharide conformations.
authors.affiliation: Departments of Pharmacology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Collins
authors.forename: M
authors.initials: M
authors.lastname: Kiso
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
authors.forename: M B
authors.initials: MB
authors.lastname: Tropak
authors.forename: J C
authors.initials: JC
authors.lastname: Roder
authors.forename: P R
authors.initials: PR
authors.lastname: Crocker
authors.forename: R L
authors.initials: RL
authors.lastname: Schnaar
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009185:Myelin Proteins / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1; D013329:Structure-Activity Relationship
chemical_list: D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D011971:Receptors, Immunologic; C104891:SMP protein, Schwann cell, Coturnix coturnix; D063267:Sialic Acid Binding Ig-like Lectin 1; D019158:N-Acetylneuraminic Acid