title: The role of valence on the high-affinity binding of Griffonia simplicifolia isolectins to type A human erythrocytes.
abstract: The Griffonia simplicifolia-I (GS-I) isolectins have been used to probe the effect of lectin valence on their high-affinity binding to human erythrocytes. These tetrameric lectins are composed of A and B subunits and constitute a series of five isolectins (A4, A3B, A2B2, AB3, B4). The A subunit is specific for alpha-D-GalNAc end groups and binds to the blood type A determinant GalNAcalpha1, as well as to terminal alpha-D-Gal groups found on type B cells. The B subunit is specific for alpha-D-Gal end groups, and binds very specifically to type B erythrocytes. This series of isolectins is tetravalent (A4), trivalent (A3B), divalent (A2B2), and monovalent (AB3) for type A erythrocytes; thus, this system provides the opportunity to examine the effect of lectin valency on the association constants of these GS-I isolectins binding to cells. Cell binding experiments carried out using 125I-labeled GS-I isolectins and type A human erythrocytes allowed us to demonstrate that (1) the association constant of the isolectin monovalent for alpha-D-GalNAc (AB3) is virtually identical to its association constant for the haptenic sugar methyl-N-acetyl-alpha-D-galactosaminide, reported previously, and (2) the association constant of the GS-I isolectins for human type A erythrocytes increases with increasing valency of the isolectin. These results indicate that the increased affinity displayed by the GS-I isolectins for human type A erythrocytes is dependent on their multivalency, and not on an extended binding site nor on nonspecific, or noncarbohydrate, interactions of the lectin with the cell surface. These findings should be of general relevance to understanding the high-affinity interactions observed between other multivalent proteins and multivalent ligands (e.g., cell surfaces).
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, Michigan 48109-0606, USA. rnkibbs@umich.edu
authors.forename: R N
authors.initials: RN
authors.lastname: Knibbs
authors.forename: M
authors.initials: M
authors.lastname: Takagaki
authors.forename: D A
authors.initials: DA
authors.lastname: Blake
authors.forename: I J
authors.initials: IJ
authors.lastname: Goldstein
mesh_terms: D000017:ABO Blood-Group System; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D037121:Plant Lectins; D011485:Protein Binding
chemical_list: D000017:ABO Blood-Group System; C045475:Griffonia simplicifolia lectins; D037102:Lectins; D037121:Plant Lectins