1CZT

CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V

1CZT の概要

• エントリーDOI: 10.2210/pdb1czt/pdb
• 関連するPDBエントリー: 1CZS 1CZV
• 分子名称: PROTEIN (COAGULATION FACTOR V) (2 entities in total)
• 機能のキーワード: coagulation, membrane-binding, discoidin family, calcium-independent, blood clotting
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted (By similarity): P12259
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18611.42

構造登録者

Macedo-Ribeiro, S.,Bode, W.,Huber, R.,Kane, W.H.,Fuentes-Prior, P. (登録日: 1999-09-07, 公開日: 1999-11-26, 最終更新日: 2024-11-13)

主引用文献

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

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: 10586886
DOI: 10.1038/46594

実験手法

X-RAY DIFFRACTION (1.87 Å)