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Interaction of Plasminogen Activator Inhibitor Type-1 (PAI-1) with Vitronectin (Vn): Mapping the Binding Sites on PAI-1 and Vn
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F. Schroeck
Published/Copyright:
June 1, 2005
Abstract
The serpin plasminogen activator inhibitor type-1 (PAI-1), as the primary physiological inhibitor of both urokinasetype (uPA) and tissuetype (tPA) plasminogen activator, plays an important role in the regulation of the fibrinolytic system as well as in extracellular remodeling in both physiological and pathophysiological processes. In plasma as well as in the extracellular matrix PAI-1 binds to vitronectin (Vn), an interaction that affects the function of both proteins. As PAI-1/Vn interaction has a significant regulatory function in fibrinolysis, thrombolysis, and cell adhesion in cancer spread, there is a strong interest in defining the binding sites on PAI-1 and Vn as the basis of a rational design of novel drugs that may modulate PAI 1/Vnmediated effects. In this minireview, we give an overview on the approaches to define the Vn binding site of PAI-1 and vice versa. Although in the case of PAI-1 the region around αhelix E and αhelix F of PAI 1 has been demonstrated to be important for its interaction with Vn, the precise location of the Vnbinding region has not completely been resolved. The major highaffinity PAI-1 binding region of Vn is localized within the Nterminal somatomedin B (SMB) domain of Vn. There are indications for at least one other lowaffinity PAI-1 binding site in the Cterminal region of Vn, which seems to be involved in the formation of larger PAI-1/Vn complexes.
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Published Online: 2005-06-01
Published in Print: 2002-08-27
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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- Secreted Aspartic Proteases as Virulence Factors of Candida Species
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- Structural Basis for the Processive Protein Degradation by Tricorn Protease
- Zinc Ligands in an Astacin Family Metalloprotease Meprin A
- Probing the Active Sites and Mechanisms of Rat Metalloproteases Meprin A and B
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