Characterization of two forms of human factor Va with different cofactor activities.

Rosing, Jan; Bakker, Harry M.; Thomassen, M. C. L. G. D.; Hemker, H. Cœnraad; Tans, Guido

doi:10.1016/s0021-9258(19)36902-9

Cited by 78 publications

(38 citation statements)

References 37 publications

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“…It was also reported (Rosing et al, 1993) that plasma factor V is heterogeneous and yields two forms of factor Va (Va 1 and Va 2 ) after activation that bind with different affinities to negatively charged membranes.…”

Section: Effect Of Phospholipid On Inactivation Of Factor Va 1 Andmentioning

confidence: 94%

“…Phospholipids were obtained from Avanti Polar Lipids, Pelham, AL. Small unilamellar phospholipid vesicles were prepared as described before (Rosing et al, 1993). S2238, S2366, and I2581 were supplied by Chromogenix, Mo ¨lndal, Sweden.…”

Section: Methodsmentioning

confidence: 99%

“…Human protein S was obtained from Enzyme Research Laboratories Inc. (Swansea, U.K.). Human factor V 1 , factor V 2 , factor Va 1 , and factor Va 2 were purified as described previously (Rosing et al, 1993).…”

Section: Methodsmentioning

confidence: 99%

“…In 1993 we reported (Rosing et al, 1993) that plasma contains two forms of factor V which likely differ in the degree of glycosylation in the carboxy-terminal C2 domain (Ortel et al, 1994a). Activation by thrombin yields two forms of factor Va (factor Va 1 and factor Va 2 ) with different affinities for procoagulant membrane surfaces and which exhibit different cofactor activities in prothrombin activation.…”

mentioning

confidence: 99%

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Human Factor Va₁ and Factor Va₂: Properties in the Procoagulant and Anticoagulant Pathways

et al. 1997

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Human plasma factor V is heterogeneous and yields two forms of activated factor V that bind with low (factor Va1) and high affinity (factor Va2) to phospholipids. The properties of factor Va1 and factor Va2 in the anticoagulant and procoagulant pathways were evaluated by comparing their sensitivity for inactivation by APC and their ability to act as cofactor in prothrombin activation. At low phospholipid concentrations and on membranes containing low amounts of phosphatidylserine (PS), factor Va1 was inactivated by APC at 15-fold lower rates than factor Va2, both in the absence and in the presence of protein S. At high phospholipid concentrations and on membranes with more than 15 mol % PS, factor Va1 and factor Va2 were inactivated with equal efficiency. Differences between cofactor activities of factor Va1 and factor Va2 in prothrombin activation were only observed on membranes with less than 7.5 mol % PS. Due to the different phospholipid requirements of APC-catalyzed factor Va inactivation and of expression of factor Va cofactor activity in prothrombin activation, the thrombin-forming capacity of factor V1 was 7-fold higher than that of factor V2 in a reaction system containing factor Xa, prothrombin, APC, protein S, vesicles with a phospholipid composition resembling that of activated platelets, and traces of thrombin to initiate prothrombin activation. This shows that in the process of generation, expression, and down-regulation of factor Va cofactor activity on physiological membranes, the overall procoagulant activity of factor V1 can considerably exceed that of factor V2.

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Section: Effect Of Phospholipid On Inactivation Of Factor Va 1 Andmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Human Factor Va₁ and Factor Va₂: Properties in the Procoagulant and Anticoagulant Pathways

et al. 1997

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“…In human plasma, FV circulates as a mixture of two isoforms, FV1 (glycosylated) and FV2 (not glycosylated) that have slightly different molecular weights because of partial N-linked glycosylation at N2181. This leads to differences in membrane-binding behavior between FV1 and FV2 (Rosing et al, 1993;Hoekema et al, 1997, Nicolaes et al, 1999. Also, glycosylation at N2181 has been proposed to modulate the FV expression levels (Nicolaes et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Theoretical and Experimental Study of the D2194G Mutation in the C2 Domain of Coagulation Factor V

Miteva

Brugge

Rosing

et al. 2004

Biophysical Journal

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Coagulation factor V (FV) is a large plasma glycoprotein with functions in both the pro- and anticoagulant pathways. In carriers of the so-called R2-FV haplotype, the FV D2194G mutation, in the C2 membrane-binding domain, is associated with low expression levels, suggesting a potential folding/stability problem. To analyze the molecular mechanisms potentially responsible for this in vitro phenotype, we used molecular dynamics (MD) and continuum electrostatic calculations. Implicit solvent simulations were performed on the x-ray structure of the wild-type C2 domain and on a model of the D2194G mutant. Because D2194 is located next to a disulfide bond (S-S bond), MD calculations were also performed on S-S bond depleted structures. D2194 is part of a salt-bridge network and investigations of the stabilizing/destabilizing role of these ionic interactions were carried out. Five mutant FV molecules were created and the expression levels measured with the aim of assessing the tolerance to amino acid changes in this region of molecule. Analysis of the MD trajectories indicated increased flexibility in some areas and energetic comparisons suggested overall destabilization of the structure due to the D2194G mutation. This substitution causes electrostatic destabilization of the domain by approximately 3 kcal/mol. Together these effects likely explain the lowered expression levels in R2-FV carriers.

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Homology Models of the C Domains of Blood Coagulation Factors V and VIII: A Proposed Membrane Binding Mode for FV and FVIII C2 Domains

Pellequer

Gale

Griffin

et al. 1998

Blood Cells, Molecules, and Diseases

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Characterization of two forms of human factor Va with different cofactor activities.

Cited by 78 publications

References 37 publications

Human Factor Va₁ and Factor Va₂: Properties in the Procoagulant and Anticoagulant Pathways

Human Factor Va₁ and Factor Va₂: Properties in the Procoagulant and Anticoagulant Pathways

Theoretical and Experimental Study of the D2194G Mutation in the C2 Domain of Coagulation Factor V

Homology Models of the C Domains of Blood Coagulation Factors V and VIII: A Proposed Membrane Binding Mode for FV and FVIII C2 Domains

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Characterization of two forms of human factor Va with different cofactor activities.

Cited by 78 publications

References 37 publications

Human Factor Va1 and Factor Va2: Properties in the Procoagulant and Anticoagulant Pathways

Human Factor Va1 and Factor Va2: Properties in the Procoagulant and Anticoagulant Pathways

Theoretical and Experimental Study of the D2194G Mutation in the C2 Domain of Coagulation Factor V

Homology Models of the C Domains of Blood Coagulation Factors V and VIII: A Proposed Membrane Binding Mode for FV and FVIII C2 Domains

Contact Info

Product

Resources

About

Human Factor Va₁ and Factor Va₂: Properties in the Procoagulant and Anticoagulant Pathways

Human Factor Va₁ and Factor Va₂: Properties in the Procoagulant and Anticoagulant Pathways