Binding of human plasminogen to basement-membrane (type IV) collagen

Abstract

Plasminogen, the zymogen form of the serine proteinase plasmin, has been implicated in numerous physiological and pathological processes involving extracellular-matrix remodelling. We have previously demonstrated that the activation of plasminogen catalysed by tissue plasminogen activator is dramatically stimulated in the presence of basement-membrane-specific type IV collagen [Stack, Gonzalez-Gronow and Pizzo (1990) Biochemistry 29, 4966-4970]. The present paper describes the binding of plasminogen to type IV collagen. Plasminogen binds to both the α1(IV) and α2(IV) chains of basement-membrane collagen with binding to the α2(IV) chain preferentially inhibited by 6-aminohexanoic acid. This binding is specific and saturable, with K(d.app.) values of 11.5 and 12.7nM for collagen and gelatin respectively. Although collagen also binds to immobilized plasminogen this interaction is unaffected by 6-aminohexanoic acid. Limited elastase proteolysis of plasminogen generated distinct collagen-binding fragments, which were identified as the kringle 1-3 and kringle 4 domains. No binding of collagen to mini-plasminogen was observed. These studies demonstrate a specific interaction between plasminogen and type IV collagen and provide further evidence for regulation of plasminogen activation by protein components of the extracellular matrix.