Summary
PDB 1CZV deposited: 1999-09-07 modified: 2009-02-24
Title CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V: DIMERIC CRYSTAL FORM
Authors Bartunik, H.D., Bode, W., Bourenkov, G.P., Fuentes-Prior, P., Huber, R., Kane, W.H., Kim, S.W., Macedo-Ribeiro, S., Ortel, T.L., Quinn-Allen, M.A., Stubbs, M.T.
Method X-RAY DIFFRACTION
Structure factors resolution 2.4 rfactor 0.205 rfree 0.257
DPI 0.73 theoretical min: 0.33
Related PDB Entries 1CZS 1CZT
Citations

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.

Nature 1999 Nov; 402(6760):434-439 doi:10.1038/46594

Cross References
Database source Identifier Description
PubMed 10586886 NATUAS
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1CZV/1 1CZV 1 monomer 0 1 0 1188
1CZV/2 1CZV 2 monomer 0 1 0 1241