1CZT
CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V
Summary for 1CZT
| Entry DOI | 10.2210/pdb1czt/pdb |
| Related | 1CZS 1CZV |
| Descriptor | PROTEIN (COAGULATION FACTOR V) (2 entities in total) |
| Functional Keywords | coagulation, membrane-binding, discoidin family, calcium-independent, blood clotting |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted (By similarity): P12259 |
| Total number of polymer chains | 1 |
| Total formula weight | 18611.42 |
| Authors | Macedo-Ribeiro, S.,Bode, W.,Huber, R.,Kane, W.H.,Fuentes-Prior, P. (deposition date: 1999-09-07, release date: 1999-11-26, Last modification date: 2024-11-13) |
| Primary citation | Macedo-Ribeiro, S.,Bode, W.,Huber, R.,Quinn-Allen, M.A.,Kim, S.W.,Ortel, T.L.,Bourenkov, G.P.,Bartunik, H.D.,Stubbs, M.T.,Kane, W.H.,Fuentes-Prior, P. Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature, 402:434-439, 1999 Cited by PubMed Abstract: 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. PubMed: 10586886DOI: 10.1038/46594 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.87 Å) |
Structure validation
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