1OC0

plasminogen activator inhibitor-1 complex with somatomedin B domain of vitronectin

Summary for 1OC0

• Entry DOI: 10.2210/pdb1oc0/pdb
• Related: 1A7C 1B3K 1C5G 1DB2 1DVM 1DVN 1LJ5 9PAI
• Descriptor: PLASMINOGEN ACTIVATOR INHIBITOR-1, VITRONECTIN (3 entities in total)
• Functional Keywords: hydrolase-inhibitor complex, serine protease inhibitor-complex, serpin, proteinase inhibitor, fibrinolysis, cell migration, plasminogen activation, heparin-binding, cell adhesion, hydrolase/inhibitor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P05121; Secreted, extracellular space: P04004
• Total number of polymer chains: 2
• Total formula weight: 48606.52

Authors

Read, R.J.,Zhou, A.,Huntington, J.A.,Pannu, N.S.,Carrell, R.W. (deposition date: 2003-02-03, release date: 2003-06-19, Last modification date: 2024-10-23)

Primary citation

Zhou, A.,Huntington, J.A.,Pannu, N.S.,Carrell, R.W.,Read, R.J.
How Vitronectin Binds Pai-1 to Modulate Fibrinolysis and Cell Migration
Nat.Struct.Biol., 10:541-, 2003

PubMed Abstract: 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.

PubMed: 12808446
DOI: 10.1038/NSB943

Experimental method

X-RAY DIFFRACTION (2.28 Å)