title: Interactions between the finger and kringle-2 domains of tissue-type plasminogen activator and plasminogen activator inhibitor-1.
abstract: We have shown that plasminogen activator inhibitor-1 (PAI-1) inhibits the fibrin binding of both the single chain and two chain forms of tissue-type plasminogen activator (tPA) through two different mechanisms. PAI-1 inhibits the finger domain-dependent fibrin binding of diisopropylfluorophosphate-inactivated single chain tPA and the kringle-2 domain-dependent fibrin binding of diisopropylfluorophosphate-inactivated two chain tPA. In accordance with the data, preformed complexes of single chain tPA/PAI-1 and of two chain tPA/PAI-1 lost the fibrin binding abilities mediated by the finger and kringle-2 domains, respectively. These effects of PAI-1 appear to be mediated by steric hindrance of the fibrin binding sites after PAI-1 binding to adjacent regions in the functional domains of tPA. We thus propose a model in which a PAI-1 binding site resides in the finger domain of a single chain, and plays a role in the reversible association of single chain tPA and PAI-1. Conformational changes may take place during the conversion of single chain tPA to two chain tPA, resulting in burying of the original PAI-1 binding site and exposure of an alternate PAI-1 binding site on the surface of the kringle-2 domain.
authors.affiliation: Division of Hemostasis and Thrombosis Research, Jichi Medical School, Tochigi.
authors.forename: M
authors.initials: M
authors.lastname: Kaneko
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: M
authors.initials: M
authors.lastname: Matsuda
authors.forename: J
authors.initials: J
authors.lastname: Mimuro
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000494:pharmacology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D015849:Plasminogen Inactivators; D005337:Fibrin; D010959:Tissue Plasminogen Activator