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

作者：D' Amico Salvino; Martial Joseph A; Struman Ingrid^*

来源：FEBS Letters, 2012, 586(6): 686-692.

DOI：10.1016/j.febslet.2012.02.013

• Plasminogen activator inhibitor-1
• Reactive centre loop
• Peptide

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 beta-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. %26lt;br%26gt;Structured summary of protein interactions: %26lt;br%26gt;PAI-1 and uPA bind by comigration in gel electrophoresis (View intera

• 出版日期2012-3-23