1oc0
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PLASMINOGEN ACTIVATOR INHIBITOR-1 COMPLEX WITH SOMATOMEDIN B DOMAIN OF VITRONECTIN
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Hemorrhagic diathesis due to PAI1 deficiency OMIM:[173360], Thrombophilia due to excessive plasminogen activator inhibitor OMIM:[173360]
About this StructureAbout this Structure
1OC0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration., Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ, Nat Struct Biol. 2003 Jul;10(7):541-4. PMID:12808446
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