Binding sites on native and multimeric vitronectin exhibit similar affinity for heparin the influence of self-association and multivalence on ligand binding.

A previously accepted model for the morphoregulatory activity of vitronectin is based on the idea that the heparin-binding site is buried within the circulating, monomeric form of vitronectin and that it is exposed on conversion to the multimeric form by denaturation or incorporation into the extracellular matrix. New evidence indicates that the heparin-binding sites are similarly exposed in the two forms of vitronectin and supports an alternative model for apparently altered heparin affinity. Differences in the heparin-binding properties of circulating and matrix-associated vitronectin result from an increased number of binding sites on the multivalent matrix form. By analogy with other instances in which multivalent binding interactions increase functional affinity for carbohydrates or lectins, the self-association of vitronectin into a multimeric form allows effective neutralization of heparin at the endothelial surface in the vicinity of a thrombus.