How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration

被引：214

作者：

Zhou, AW ^{[1
]}

Huntington, JA ^{[1
]}

Pannu, NS ^{[1
]}

Carrell, RW ^{[1
]}

Read, RJ ^{[1
]}

机构：

[1] Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 2XY, England

来源：

NATURE STRUCTURAL BIOLOGY | 2003年 / 10卷 / 07期

基金：

美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1038/nsb943

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The interaction of the plasma protein vitronectin with plasminogen activator inhibitor-1 (PAI-1) is central to human health. Vitronectin binding extends the lifetime of active PAI-1, which controls hemostasis by inhibiting fibrinolysis and has also been implicated in angiogenesis. The PAI-1 vitronectin binding interaction also affects cell adhesion and motility. For these reasons, elevated PAI-1 activities are associated both with coronary thrombosis and with a poor prognosis in many cancers. Here we show the crystal structure at a resolution of 2.3 Angstrom of the complex of the somatomedin B domain of vitronectin with PAI-1. The structure of the complex explains how vitronectin binds to and stabilizes the active conformation of PAI-1. It also explains the tissue effects of PAI-1, as PAI-1 competes for and sterically blocks the interaction of vitronectin with cell surface receptors and integrins. Structural understanding of the essential biological roles of the interaction between PAI-1 and vitronectin opens the prospect of specifically designed blocking agents for the prevention of thrombosis and treatment of cancer.

引用

页码：541 / 544

页数：4

共 33 条

[31] Use of TLS parameters to model anisotropic displacements in macromolecular refinement [J].

Winn, MD ;

Isupov, MN ;

Murshudov, GN .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2001, 57 :122-133

[32] Crystal structure of the extracellular segment of integrin αVβ3 in complex with an Arg-Gly-Asp ligand [J].

Xiong, JP ;

Stehle, T ;

Zhang, RG ;

Joachimiak, A ;

Frech, M ;

Goodman, SL ;

Arnaout, MA .

SCIENCE, 2002, 296 (5565) :151-155

[33] Characterization of the ligand binding activities of vitronectin: Interaction of vitronectin with lipids and identification of the binding domains for various ligands using recombinant domains [J].

Yoneda, A ;

Ogawa, H ;

Kojima, K ;

Matsumoto, I .

BIOCHEMISTRY, 1998, 37 (18) :6351-6360

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