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. 1989 Feb 1;257(3):679–683. doi: 10.1042/bj2570679

The interaction between human blood-coagulation factor VIII and von Willebrand factor. Characterization of a high-affinity binding site on factor VIII.

A Leyte 1, M P Verbeet 1, T Brodniewicz-Proba 1, J A Van Mourik 1, K Mertens 1
PMCID: PMC1135641  PMID: 2494987

Abstract

The interaction between human Factor VIII and immobilized multimeric von Willebrand Factor (vWF) was characterized. Equilibrium binding studies indicated the presence of multiple classes of Factor VIII-binding sites on vWF. The high-affinity binding (Kd = 2.1 x 10(-10) M) was restricted to only 1-2% of the vWF subunits. Competition studies with monoclonal antibodies with known epitopes demonstrated that the Factor VIII sequence Lys1673-Arg1689 is involved in the high-affinity interaction with vWF.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson L. O., Forsman N., Huang K., Larsen K., Lundin A., Pavlu B., Sandberg H., Sewerin K., Smart J. Isolation and characterization of human factor VIII: molecular forms in commercial factor VIII concentrate, cryoprecipitate, and plasma. Proc Natl Acad Sci U S A. 1986 May;83(9):2979–2983. doi: 10.1073/pnas.83.9.2979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Brinkhous K. M., Sandberg H., Garris J. B., Mattsson C., Palm M., Griggs T., Read M. S. Purified human factor VIII procoagulant protein: comparative hemostatic response after infusions into hemophilic and von Willebrand disease dogs. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8752–8756. doi: 10.1073/pnas.82.24.8752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Eaton D., Rodriguez H., Vehar G. A. Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochemistry. 1986 Jan 28;25(2):505–512. doi: 10.1021/bi00350a035. [DOI] [PubMed] [Google Scholar]
  5. Fay P. J. Reconstitution of human factor VIII from isolated subunits. Arch Biochem Biophys. 1988 May 1;262(2):525–531. doi: 10.1016/0003-9861(88)90404-3. [DOI] [PubMed] [Google Scholar]
  6. Foster P. A., Fulcher C. A., Houghten R. A., Zimmerman T. S. An immunogenic region within residues Val1670-Glu1684 of the factor VIII light chain induces antibodies which inhibit binding of factor VIII to von Willebrand factor. J Biol Chem. 1988 Apr 15;263(11):5230–5234. [PubMed] [Google Scholar]
  7. Foster P. A., Fulcher C. A., Marti T., Titani K., Zimmerman T. S. A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. J Biol Chem. 1987 Jun 25;262(18):8443–8446. [PubMed] [Google Scholar]
  8. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  9. Girma J. P., Meyer D., Verweij C. L., Pannekoek H., Sixma J. J. Structure-function relationship of human von Willebrand factor. Blood. 1987 Sep;70(3):605–611. [PubMed] [Google Scholar]
  10. Hamer R. J., Koedam J. A., Beeser-Visser N. H., Bertina R. M., Van Mourik J. A., Sixma J. J. Factor VIII binds to von Willebrand factor via its Mr-80,000 light chain. Eur J Biochem. 1987 Jul 1;166(1):37–43. doi: 10.1111/j.1432-1033.1987.tb13480.x. [DOI] [PubMed] [Google Scholar]
  11. Kane W. H., Davie E. W. Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood. 1988 Mar;71(3):539–555. [PubMed] [Google Scholar]
  12. Lollar P., Hill-Eubanks D. C., Parker C. G. Association of the factor VIII light chain with von Willebrand factor. J Biol Chem. 1988 Jul 25;263(21):10451–10455. [PubMed] [Google Scholar]
  13. Lollar P., Parker C. G. Stoichiometry of the porcine factor VIII-von Willebrand factor association. J Biol Chem. 1987 Dec 25;262(36):17572–17576. [PubMed] [Google Scholar]
  14. Marti T., Rösselet S. J., Titani K., Walsh K. A. Identification of disulfide-bridged substructures within human von Willebrand factor. Biochemistry. 1987 Dec 15;26(25):8099–8109. doi: 10.1021/bi00399a013. [DOI] [PubMed] [Google Scholar]
  15. Mertens K., van Wijngaarden A., Bertina R. M. The role of factor VIII in the activation of human blood coagulation factor X by activated factor IX. Thromb Haemost. 1985 Oct 30;54(3):654–660. [PubMed] [Google Scholar]
  16. Over J., Sixma J. J., Bouma B. N., Bolhuis P. A., Vlooswijk R. A., Beeser-Visser N. H. Survival of iodine-125-labeled factor VIII in patients with von Willebrand's disease. J Lab Clin Med. 1981 Mar;97(3):332–344. [PubMed] [Google Scholar]
  17. Reinders J. H., Vervoorn R. C., Verweij C. L., van Mourik J. A., de Groot P. G. Perturbation of cultured human vascular endothelial cells by phorbol ester or thrombin alters the cellular von Willebrand factor distribution. J Cell Physiol. 1987 Oct;133(1):79–87. doi: 10.1002/jcp.1041330110. [DOI] [PubMed] [Google Scholar]
  18. Rosén S., Andersson M., Blombäck M., Hägglund U., Larrieu M. J., Wolf M., Boyer C., Rothschild C., Nilsson I. M., Sjörin E. Clinical application of a chromogenic substrate method for determination of factor VIII activity. Thromb Haemost. 1985 Dec 17;54(4):818–823. [PubMed] [Google Scholar]
  19. Rotblat F., O'Brien D. P., O'Brien F. J., Goodall A. H., Tuddenham E. G. Purification of human factor VIII:C and its characterization by Western blotting using monoclonal antibodies. Biochemistry. 1985 Jul 30;24(16):4294–4300. doi: 10.1021/bi00337a007. [DOI] [PubMed] [Google Scholar]
  20. Stel H. V., Sakariassen K. S., Scholte B. J., Veerman E. C., van der Kwast T. H., de Groot P. G., Sixma J. J., van Mourik J. A. Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium. Blood. 1984 Jun;63(6):1408–1415. [PubMed] [Google Scholar]
  21. Takahashi Y., Kalafatis M., Girma J. P., Sewerin K., Andersson L. O., Meyer D. Localization of a factor VIII binding domain on a 34 kilodalton fragment of the N-terminal portion of von Willebrand factor. Blood. 1987 Nov;70(5):1679–1682. [PubMed] [Google Scholar]
  22. Toole J. J., Knopf J. L., Wozney J. M., Sultzman L. A., Buecker J. L., Pittman D. D., Kaufman R. J., Brown E., Shoemaker C., Orr E. C. Molecular cloning of a cDNA encoding human antihaemophilic factor. Nature. 1984 Nov 22;312(5992):342–347. doi: 10.1038/312342a0. [DOI] [PubMed] [Google Scholar]
  23. Veerman E. C., Stel H. V., Huisman J. G., van Mourik J. A. Application of sepharose-linked monoclonal antibodies for the immunoradiometric measurement of factor VIII-procoagulant antigen. Thromb Res. 1984 Jan 1;33(1):89–93. doi: 10.1016/0049-3848(84)90157-9. [DOI] [PubMed] [Google Scholar]
  24. Vehar G. A., Keyt B., Eaton D., Rodriguez H., O'Brien D. P., Rotblat F., Oppermann H., Keck R., Wood W. I., Harkins R. N. Structure of human factor VIII. Nature. 1984 Nov 22;312(5992):337–342. doi: 10.1038/312337a0. [DOI] [PubMed] [Google Scholar]
  25. Wagner D. D., Marder V. J. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol. 1984 Dec;99(6):2123–2130. doi: 10.1083/jcb.99.6.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. van Dieijen G., Tans G., Rosing J., Hemker H. C. The role of phospholipid and factor VIIIa in the activation of bovine factor X. J Biol Chem. 1981 Apr 10;256(7):3433–3442. [PubMed] [Google Scholar]

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