Article (Scientific journals)
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
D'Amico, Salvino; Martial, Joseph; Struman, Ingrid
2012In FEBS Letters, 586, p. 686-692
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Keywords :
Plasminogen activator inhibitor-1; Reactive Centre Loop; peptide
Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
D'Amico, Salvino ;  Université de Liège - ULiège > GIGA-Research
Martial, Joseph ;  Université de Liège - ULiège > Département des sciences de la vie > Département des sciences de la vie
Struman, Ingrid  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
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
Publication date :
2012
Journal title :
FEBS Letters
ISSN :
0014-5793
eISSN :
1873-3468
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
586
Pages :
686-692
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 20 January 2012

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