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1czv
From Proteopedia
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CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V: DIMERIC CRYSTAL FORM
Contents |
Overview
Rapid and controlled clot formation is achieved through sequential, activation of circulating serine proteinase precursors on, phosphatidylserine-rich procoagulant membranes of activated platelets and, endothelial cells. The homologous complexes Xase and prothrombinase, each, consisting of an active proteinase and a non-enzymatic cofactor, perform, critical steps within this coagulation cascade. The activated cofactors, VIIIa and Va, highly specific for their cognate proteinases, are each, derived from precursors with the same A1-A2-B-A3-C1-C2 architecture., Membrane binding is mediated by the C2 domains of both cofactors. Here we, report two crystal structures of the C2 domain of human factor Va. The, conserved beta-barrel framework provides a scaffold for three protruding, loops, one of which adopts markedly different conformations in the two, crystal forms. We propose a mechanism of calcium-independent, stereospecific binding of factors Va and VIIIa to phospholipid membranes, on the basis of (1) immersion of hydrophobic residues at the apices of, these loops in the apolar membrane core; (2) specific interactions with, phosphatidylserine head groups in the groove enclosed by these loops; and, (3) favourable electrostatic contacts of basic side chains with negatively, charged membrane phosphate groups.
Disease
Known diseases associated with this structure: Budd-Chiari syndrome OMIM:[227400], Hemorrhagic diathesis due to factor V deficiency OMIM:[227400], Thromboembolism susceptibility due to factor V Leiden OMIM:[227400], Thrombophilia due to factor V Liverpool OMIM:[227400]
About this Structure
1CZV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of the membrane-binding C2 domain of human coagulation factor V., Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior P, Nature. 1999 Nov 25;402(6760):434-9. PMID:10586886
Page seeded by OCA on Mon Nov 12 16:27:07 2007
