PDBsum entry: 1czs

Blood clotting

PDB-id: 1czs

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Description

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Header records

References

PROCHECK

Protein chain

160 a.a. *

Ligands

PHG

Waters ×133

* Residue conservation analysis

Tools

Clefts Calculation

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PDB id:

1czs

Name:

Blood clotting

Title:

Crystal structure of the c2 domain of human coagulation factor v: complex with phenylmercury

Structure:

Protein (coagulation factor v). Chain: a. Fragment: c2 discoidin-like domain. Synonym: activated protein c cofactor. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. System

UniProt:

P12259 (FA5_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

2224 a.a.

Struc:

160 a.a.*

Key:	PfamA domain	PfamB domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

Resolution:

1.90Å

R-factor:

0.196

R-free:

0.258

Authors:

S.Macedo-Ribeiro,W.Bode,R.Huber,W.H.Kane,P.Fuentes-Prior

Key ref:

S.Macedo-Ribeiro et al. (1999). Crystal structures of the membrane-binding C2 domain of human coagulation factor V.. Nature, 402, 434-439. [PubMed id: 10586886] [DOI: 10.1038/46594]

Date:

07-Sep-99

Release date:

26-Nov-99

Related entries:

1czt
1czv

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Clefts

Surface

Key reference

DOI no: 10.1038/46594

Nature 402:434-439 (1999)

PubMed id: 10586886

Crystal structures of the membrane-binding C2 domain of human coagulation factor V.

S.Macedo-Ribeiro, W.Bode, R.Huber, M.A.Quinn-Allen, S.W.Kim, T.L.Ortel, G.P.Bourenkov, H.D.Bartunik, M.T.Stubbs, W.H.Kane, P.Fuentes-Prior.

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.

Selected figure(s)

Figure 3.
Figure 3 Conformational flexibility in the spike region. a, Stereo view of the FVa-C2 structures, superimposed in the same orientation as in Fig. 1. The open form is shown in green. The closed form is displayed in yellow, with several side chains colour-coded (carbon, yellow; oxygen, red; nitrogen, blue). b, c, GRASP30 surface representations of the electrostatic potential (red, negative; blue, positive) of FVa-C2 in the closed (b) and in the open (c) crystal form. The view is from the membrane side, that is, perpendicular to the reference orientation.

Figure 5.
Figure 5 Structural basis of the stereospecific recognition of P[L]S by FVa-C2. a, Predicted hydrogen-bond interactions (dashed red lines) inside the major P[L]S-binding site. b, Stereo view of the 'open', membrane-competent form of FVa-C2 with five P[L]S molecules bound to the proposed anchoring points in the spike region. Relevant side chains are labelled; bound phospholipid molecules are shown as space-filling models.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1999, 402, 434-439) copyright 1999.

Figures were selected by the author.