title: Monovalent interactions of galectin-1.
abstract: Galectin-1, a β-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much on the dimeric state of galectin-1 and thus is due mainly to monomeric interactions of a single carbohydrate recognition domain. The mechanism for this is unknown, but one possibility includes additional interactions that high-affinity ligands make with an extended binding site on the carbohydrate recognition domain. It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors.
authors.affiliation: Institute of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Salomonsson
authors.forename: Amaia
authors.initials: A
authors.lastname: Larumbe
authors.forename: Johan
authors.initials: J
authors.lastname: Tejler
authors.forename: Erik
authors.initials: E
authors.lastname: Tullberg
authors.forename: Hanna
authors.initials: H
authors.lastname: Rydberg
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Areej
authors.initials: A
authors.lastname: Khabut
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Frejd
authors.forename: Yuri D
authors.initials: YD
authors.lastname: Lobsanov
authors.forename: James M
authors.initials: JM
authors.lastname: Rini
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D018360:Crystallography, X-Ray; D060748:Fetuins; D005454:Fluorescence Polarization; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D051381:Rats; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D001212:Asialoglycoproteins; D001798:Blood Proteins; D060748:Fetuins; D037483:Galectin 1; D006023:Glycoproteins; D000509:alpha-Fetoproteins; C017029:asialofetuin