Effects of clustered epitopes in multivalent ligand-receptor interactions.
Many biological ligands are composed of clustered binding epitopes. However, the effects of clustered epitopes on the affinity of ligand-receptor interactions in many cases are not well understood. Clustered carbohydrate epitopes are present in naturally occurring multivalent carbohydrates and glycoproteins, which are receptors on the surface of cells. Recent studies have provided evidence that the enhanced affinities of lectins, which are carbohydrate binding proteins, for multivalent carbohydrates and glycoproteins are due to internal diffusion of lectin molecules from epitope to epitope in these multivalent ligands before dissociation. Indeed, binding of lectins to mucins, which are large linear glycoproteins, appears to be similar to the internal diffusion mechanism(s) of protein ligands binding to DNA, which have been termed the "bind and slide" or "bind and hop" mechanisms. The observed increasing negative cooperativity and gradient of decreasing microaffinity constants of a lectin binding to multivalent carbohydrates and glycoproteins result in an initial fraction of lectin molecules that bind with very high affinity and dynamic motion. These findings have important implications for the mechanisms of binding of lectins to mucins, and for other ligand-biopolymer interactions and clustered ligand-receptor systems in general.
Dam
Tarun K
TK
Department of Molecular Pharmacology and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Brewer
C Fred
CF
D001212:Asialoglycoproteins / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D000939:Epitopes; D060748:Fetuins; D037161:Galectins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D000509:alpha-Fetoproteins / Q000737:chemistry / Q000378:metabolism
D001212:Asialoglycoproteins; D000939:Epitopes; D060748:Fetuins; D037161:Galectins; D008024:Ligands; D000509:alpha-Fetoproteins; C017029:asialofetuin; D004247:DNA