title: A peptide mimicking the C-terminal part of the reactive center loop induces the transition to the latent form of plasminogen activator inhibitor type-1.
abstract: Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of plasminogen activators (uPA and tPA) and thus plays a central role in fibrinolysis. The spontaneous insertion of its reactive centre loop (RCL) into β-sheet A is responsible for its irreversible conversion into the inactive latent form. In this study, we used two peptides mimicking residues P14-P9 and P8-P3 of the RCL so as to understand this dynamic process. We show that both peptides inhibit the formation of PAI-1/uPA and PAI-1/tPA complexes via two different mechanisms. Targeting the N-terminal part of the loop induces the cleavage of PAI-1 by the proteases uPA/tPA while targeting its C-terminal part greatly favors the irreversible formation of latent PAI-1.
authors.affiliation: Molecular Biology and Genetic Engineering Unit, GIGA-Research, B34, 1 Avenue de l'Hôpital, Université de Liège, Sart-Tilman, Belgium.
authors.forename: Salvino
authors.initials: S
authors.lastname: D'Amico
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.forename: Ingrid
authors.initials: I
authors.lastname: Struman
mesh_terms: D020134:Catalytic Domain; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator