1oc0: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1oc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oc0 OCA], [http://www.ebi.ac.uk/pdbsum/1oc0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1oc0 RCSB]</span> | |||
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==Overview== | ==Overview== | ||
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 A 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. | 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 A 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Read, R J.]] | [[Category: Read, R J.]] | ||
[[Category: Zhou, A.]] | [[Category: Zhou, A.]] | ||
[[Category: cell migration]] | [[Category: cell migration]] | ||
[[Category: fibrinolysis]] | [[Category: fibrinolysis]] | ||
[[Category: heparin-binding | [[Category: plasminogen activation,heparin-binding,cell adhesion]] | ||
[[Category: proteinase inhibitor]] | [[Category: proteinase inhibitor]] | ||
[[Category: serpin]] | [[Category: serpin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:42:59 2008'' | ||