1czt
From Proteopedia
(New page: 200px<br /> <applet load="1czt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1czt, resolution 1.87Å" /> '''CRYSTAL STRUCTURE O...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1czt.gif|left|200px]]<br /> | + | [[Image:1czt.gif|left|200px]]<br /><applet load="1czt" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1czt" size=" | + | |
caption="1czt, resolution 1.87Å" /> | caption="1czt, resolution 1.87Å" /> | ||
'''CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V'''<br /> | '''CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Rapid and controlled clot formation is achieved through sequential | + | 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== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1CZT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1CZT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CZT OCA]. |
==Reference== | ==Reference== | ||
| Line 20: | Line 19: | ||
[[Category: Fuentes-Prior, P.]] | [[Category: Fuentes-Prior, P.]] | ||
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
| - | [[Category: Kane, W | + | [[Category: Kane, W H.]] |
[[Category: Macedo-Ribeiro, S.]] | [[Category: Macedo-Ribeiro, S.]] | ||
[[Category: blood clotting]] | [[Category: blood clotting]] | ||
| Line 28: | Line 27: | ||
[[Category: membrane-binding]] | [[Category: membrane-binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:11:28 2008'' |
Revision as of 10:11, 21 February 2008
|
CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V
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
1CZT 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 Thu Feb 21 12:11:28 2008
