|
 MULTIMERIC STRUCTURE OF VON WILLEBRAND FACTOR
The formation of a 1.8 MDa von Willebrand factor (vWF) multimer with bound
factor VIII is illustrated. Each vWF monomer (Mr=260,000) contains a factor VIII binding
site near the NH2-terminal end of the molecule. The monomers are joined
end-to-end (NH2 to NH2 and COOH to COOH) by disulfide bonds to form
large multimers. The mature multimers can bind one factor VIII molecule per monomeric
subunit.
Von Willebrand factor (vWF) is a multimeric plasma glycoprotein that is required for normal hemostatic platelet plug formation (1-8). The mature plasma protein is composed of apparently identical subunits (Mr=260,000) which are held together by disulfide bonds. The circulating vWF molecule ranges in size from dimers (Mr=520,000) to extremely large multimers (Mr>10,000,000). During normal hemostasis, the larger multimers of vWF are responsible for facilitating platelet plug formation by forming a bridge between platelet glycoprotein IB and exposed collagen in the subendothelium (9-14). Either a lack of vWF protein or the presence of abnormalities which result in decreased polymerization may cause a loss of biological activity which is characteristic of von Willebrand's disease.
In addition to its role in platelet plug formation, vWF is also responsible for the binding and transport of factor VIII (antihemophilic factor) in plasma (15). It appears that this latter event is responsible for both the stability and effective delivery of functional factor VIII. Studies indicate that factor VIII binds to the NH2-terminal portion of the mature vWF subunit with a stoichiometry of one factor VIII molecule per vWF monomer (16,17).
The single chain vWF monomer contains a large number of cysteine residues at both the
NH2-terminal and COOH-terminal ends, which are involved in the multimer formation. Carbohydrate analyses indicate that nearly 15% of the mass of vWF is contributed by carbohydrate (18). It appears that the carbohydrate serves to protect vWF from proteolysis, but is not necessary for functional activity or multimer formation.
vWF is prepared from citrated human plasma using a combination of the procedures described by Thorell (19), and Lollar (20). A factor VIII free vWF preparation, further purified to ensure removal of factor VIII procoagulant activity, is also available. The preparations are >95% pure as judged by SDS-PAGE under reducing conditions, and consist of large multimers as determined by electrophoresis in SDS/agarose gels. The protein is shipped frozen in 0.025M sodium citrate, 0.1M glycine, 0.1M NaCl, pH 6.8, for storage at -70°C.
|
Properties
of von Willebrand Factor |
|
Localization:
|
Plasma and subendothelium |
|
Mode of action:
|
facilitates platelet plug formation by forming a bridge between platelet glycoprotein
IB and exposed collagen in the subendothelium; also binds and transports factor VIII |
|
Molecular weight:
|
260,000 to >10,000,000 (1-8) |
|
Isoelectric
point:
|
5.7-5.9
(21) |
|
Extinction coefficient:
|
Not Applicable; concentration determined by total protein assay. |
|
Concentration
in plasma
|
10
micrograms/mL (21) |
|
Structure:
|
multimeric protein composed of identical 260,000 molecular weight subunits |
|
Percent carbohydrate:
|
approximately 15% (18) |
|
Catalog
Number |
Description |
|
HCVWF-0190 |
Human von Willebrand
Factor |
|
HCVWF-0191 |
Human von Willebrand
Factor - Factor VIII Free |
PRICING
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ABOUT THIS PRODUCT
References
1. Hoyer, L.W., Blood, 58, 1 (1981).
2. Ruggeri, Z.M. and Zimmerman, T.S., J. Clin. Invest., 65, 1318 (1980).
3. Zimmerman, T.S., et al., Proc. Natl. Acad. Sci. USA, 72, 5121 (1975).
4. Hoyer, L.W. and Shainoff, J.R., Blood, 55, 1056 (1980).
5. Counts, R.B., et al., J. Clin. Invest., 62, 702 (1979).
6. Perret, B.A., et al., Biochim. Biophys. Acta, 578, 164 (1979).
7. Weinstein, M. and Deykin, D., Blood, 53, 1095 (1979).
8. Meyer, D., et al., J. Lab. Clin. Invest., 95, 590 (1980).
9. Okumura, T. and Jameison, G.A., Thromb. Res., 8, 701 (1976).
10. Nachman, R.L., et al., J. Clin. Invest., 59, (1977).
11. Jenkins, C.S.P., et al., J. Clin. Invest., 57, 112 (1976).
12. Santoro, S.A., Thromb. Res., 21, 689 (1981).
13. Santoro, S.A. and Cowan, J.F., Collagen Relat. Res., 2, 31 (1982).
14. Morton, L.F., et al., Thromb. Res., 32, 545 (1983).
15. Tuddenham, E.G.D., et al., Br. J. Haematol., 52, 259 (1982).
16. Foster, P.A., et al., J. Biol. Chem., 262, 8443 (1987).
17. Parker, C.G. and Lollar, P., J. Biol. Chem., 262, 17572 (1987).
18. Federici, A.B., et al., J. Clin. Invest., 74, 2049 (1984).
19. Thorell, L. and Blomback, B., Thromb. Res., 35, 431 (1984).
20. Lollar, P., et al., J. Biol. Chem., 263, 10451 (1988).
21.
Furlan, M., Human Protein Data (A. Haeberli, ed.) © VCH Verlagsges, mbH,
Weinheim
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