Download PDF
Thromb Haemost 1992; 67(06): 594-599
DOI: 10.1055/s-0038-1648506
Review Articles
Schattauer GmbH Stuttgart

The Structure and Function of von Willebrand Factor

Zaverio M Ruggeri
The Roon Research Laboratory for Arteriosclerosis and Thrombosis, Division of Experimental Thrombosis and Hemostasis, Department of Molecular and Experimental Medicine and Committee on Vascular Biology, The Scripps Research Institute, La Jolla, CA, U.S. A.
,
Jerry Ware
The Roon Research Laboratory for Arteriosclerosis and Thrombosis, Division of Experimental Thrombosis and Hemostasis, Department of Molecular and Experimental Medicine and Committee on Vascular Biology, The Scripps Research Institute, La Jolla, CA, U.S. A.
› Author Affiliations
Further Information

Publication History

Received 19 August 1991

Accepted after revision 12 February 1992

Publication Date:
03 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints
 

  • References

  • 1 Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation of classic hemophilia (Factor VIII deficiency) and von Wille-brand’s disease. With observations on combined deficiencies of antihemophilic factor and proaccelerin (Factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest 1971; 40: 244-254
    PubMedGoogle Scholar
  • 2 Bonthron DT, Handin RI, Kaufman RJ, Wasley LC, Orr EC, Mitsock LM, Ewenstein B, Loscalzo J, Ginsburg D, Orkin SH. Structure of pre-pro-von Willebrand factor and its expression in heterologous cells. Nature 1986; 324: 270-273
    CrossrefPubMedGoogle Scholar
  • 3 Marti T, Roesselet S, Titani K, Walsh KA. Identification of disulfide-bridged substructures within human von Willebrand factor. Biochemistry 1987; 26: 8099-8109
    CrossrefPubMedGoogle Scholar
  • 4 Fowler WE, Fretto LJ. Electron Microscopy of von Willebrand Factor. In: Coagulation and Bleeding Disorders. The Role of Factor VIII and von Willebrand Factor. Zimmerman TS, Ruggeri ZM. (eds) Marcel Dekker, Inc.; New York; 1989. pp 181-193
    Google Scholar
  • 5 Wagner DD, Lawrence SO, Ohlsson-Wilhelm BM, Fay PJ, Marder VJ. Topology and order of formation of interchain disulfide bonds in von Willebrand factor. Blood 1987; 69: 27-32
    CrossrefPubMedGoogle Scholar
  • 6 Voorberg J, Fontijn R, van Mourik JA, Pannekoek H. Domains involved in multimer assembly of von Willebrand factor (vWF): multimerization is independent of dimerization. EMBO J 1990; 9: 797-803
    PubMedGoogle Scholar
  • 7 Voorberg J, Fontijn R, Calafat J, Janssen H, van Mourik JA, Pannekoek H. Assembly and routing of von Willebrand factor variants: The requirements for disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids. J Cell Biol 1991; 113: 195-205
    CrossrefPubMedGoogle Scholar
  • 8 Azuma H, Dent JA, Sugimoto M, Ruggeri ZM, Ware J. Independent Assembly and Secretion of a Dimeric Adhesive Domain of von Willebrand Factor Containing the Glycoprotein Ib-Binding Site. J Biol Chem 1991; 266: 12342-12347
    PubMedGoogle Scholar
  • 9 Ware J, Dent JA, Azuma H, Sugimoto M, Kyrle PA, Yoshioka A, Ruggeri ZM. Identification of a point mutation in Type IIB von Willebrand Disease illustrating the regulation of von Willebrand Factor affinity for the platelet GP Ib-IX receptor. Proc Natl Acad Sci USA 1991; 88: 2946-2950
    CrossrefPubMedGoogle Scholar
  • 10 Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, Walsh KA, Chopek MW, Sadler JE, Fujikawa K. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25: 3171-3184
    CrossrefPubMedGoogle Scholar
  • 11 Carew JA, Browning PJ, Lynch DC. Sulfation of von Willebrand Factor. Blood 1990; 76: 2530-2539
    PubMedGoogle Scholar
  • 12 Wagner DD, Mayadas T, Marder VJ. Initial glycosylation and acidic pH in the Golgi apparatus are required for multimerization of von Willebrand factor. J Cell Biol 1986; 102: 1320-1324
    CrossrefPubMedGoogle Scholar
  • 13 Bloom AL, Giddings JC, Wilks CJ. Factor VIII on the vascular intima: possible importance in haemostasis and thrombosis. Nature 1973; 241: 217-219
    CrossrefPubMedGoogle Scholar
  • 14 Koutts J, Walsh PN, Plow EF, Fenton JW, Bouma BN, Zimmerman TS. Active release of human platelet Factor VUI-related antigen by adenosine diphosphate, collagen and thrombin. J Clin Invest 1978; 62: 1255-1263
    CrossrefPubMedGoogle Scholar
  • 15 Fay PJ, Kawai Y, Wagner DD, Ginsburg D, Bonthron D, Ohlsson-Wilhelm BM, Chavin SI, Abraham GN, Handin RI, Orkin SH, Montgomery RR, Marder VJ. Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II. Science 1986; 232: 995-998
    CrossrefPubMedGoogle Scholar
  • 16 Wagner DD, Fay PJ, Sporn LA, Sinha S, Lawrence SO, Marder VJ. Divergent fates of von Willebrand factor and its propolypeptide (von Willebrand antigen II) after secretion from endothelial cells. Proc Natl Acad Sci USA 1987; 84: 1955-1959
    CrossrefPubMedGoogle Scholar
  • 17 Montgomery RR, Dent J, Schmidt W, Kyrle P, Niessner H, Ruggeri ZM, Zimmerman TS. Hereditary persistence of circulating pro von Willebrand factor (pro-vWf). Circulation 1986; 74: II1-406a
    CrossrefPubMedGoogle Scholar
  • 18 Dent JA, Berkowitz SD, Ware J, Kasper CK, Ruggeri ZM. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor. Proc Natl Acad Sci USA 1990; 87: 6306-6310
    CrossrefPubMedGoogle Scholar
  • 19 Weiss HJ, Hawiger J, Ruggeri ZM, Turitto VT, Thiagarajan P, Hoffmann T. Fibrinogen-independent platelet adhesion and thrombus formation on subendothelium mediated by glycoprotein IIb-IIIa complex at high shear rate. J Clin Invest 1989; 83: 288-297
    CrossrefPubMedGoogle Scholar
  • 20 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VUI/von Willebrand factor bound to the subendothelium. Nature 1979; 279: 636-638
    CrossrefPubMedGoogle Scholar
  • 21 de Groot PG, Ottenhof-Rovers M, van Mourik JA, Sixma JJ. rEvidence that the primary binding site of von Willebrand factor that mediates platelet adhesion on subendothelium is not collagen. J Clin Invest 1988; 82: 65-73
    CrossrefPubMedGoogle Scholar
  • 22 Ruggeri ZM, De Marco L, Gatti L, Bader R, Montgomery RR. Platelets have more than one binding site for von Willebrand factor. J Clin Invest 1983; 72: 1-12
    CrossrefPubMedGoogle Scholar
  • 23 De Marco L, Girolami A, Russell S, Ruggeri ZM. Interaction of asialo von Willebrand factor with glycoprotein lb induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation. J Clin Invest 1985; 75: 1198-1203
    CrossrefPubMedGoogle Scholar
  • 24 Sakariassen KS, Nievelstein PF, Coller BS, Sixma JJ. The role of platelet membrane glycoproteins lb and IIb-IIIa in platelet adherence to human artery subendothelium. Br J Haematol 1986; 63: 681-691
    CrossrefPubMedGoogle Scholar
  • 25 Ikeda Y, Handa M, Kawano K, Kamata T, Murata M, Araki Y, Anbo H, Kawai Y, Watanabe K, Itagaki I, Sakai K, Ruggeri ZM. The role of von Willebrand Factor and fibrinogen in platelet aggregation under varying shear stress. J Clin Invest 1991; 87: 1234-1240
    CrossrefPubMedGoogle Scholar
  • 26 Howard MA, Firkin BG. Ristocetin - A new tool in the investigation of platelet aggregation. Thromb Haemostas 1971; 26: 362-369
    PubMedGoogle Scholar
  • 27 Read MS, Smith SV, Lamb MA, Brinkhous KM. Role of botrocetin in platelet agglutination: formation of an activated complex of botrocetin and von Willebrand factor. Blood 1989; 74: 1031-1035
    PubMedGoogle Scholar
  • 28 Sugimoto M, Mohri H, McClintock RA, Ruggeri ZM. Identification of discontinuous von Willebrand factor sequences involved in complex formation with Botrocetin: a model for the regulation of von Willebrand factor binding to platelet glycoprotein lb. J Biol Chem 1991; 266: 18172-18178
    PubMedGoogle Scholar
  • 29 Fujimoto T, Hawiger J. Adenosine diphosphate induces binding of von Willebrand factor to human platelets. Nature 1982; 297: 154-156
    CrossrefPubMedGoogle Scholar
  • 30 Fujimoto T, Ohara S, Hawiger J. Thrombin-induced exposure and prostacyclin inhibition of the receptor for factor VUI/von Willebrand factor on human platelets. J Clin Invest 1982; 69: 1212-1222
    CrossrefPubMedGoogle Scholar
  • 31 Ruggeri ZM, Bader R, De Marco L. Glanzmann thrombasthenia: Deficient binding of von Willebrand factor to thrombin-stimulated platelets. Proc Natl Acad Sci USA 1982; 79: 6038-6041
    CrossrefPubMedGoogle Scholar
  • 32 Pietu G, Cherel G, Marguerie G, Meyer D. Inhibition of von Willebrand factor-platelet interaction by fibrinogen. Nature 1984; 308: 648-649
    CrossrefPubMedGoogle Scholar
  • 33 Peterson DM, Stathopoulos NA, Giorgio TD, Heliums JD, Moake JL. Shear-induced platelet aggregation requires von Willebrand factor and platelet membrane glycoproteins lb and IIb-IIIa. Blood 1987; 69: 625-628
    PubMedGoogle Scholar
  • 34 Colombatti A, Bonaldo P. The superfamily of proteins with von Willebrand factor type A-like domains: One theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms. Blood 1991; 77: 2305-2315
    PubMedGoogle Scholar
  • 35 Roth GJ, Titani K, Hoyer LW, Hickey MJ. Localization of binding sites within human von Willebrand factor for monomeric Type III collagen. Biochemistry 1986; 25: 8357-8361
    CrossrefPubMedGoogle Scholar
  • 36 Andrews RK, Gorman JJ, Booth WJ, Corino GL, Castaldi PA, Bemdt MC. Cross-linking of a monomeric 39/34-kDa dispase fragment of von Willebrand factor (Leu-480/Val-481-Gly-718) to the N-terminal region of the a-chain of membrane glycoprotein lb on intact platelets with Bis(sulfosuccinimidyl) suberate. Biochemistry 1989; 28: 8326-8336
    CrossrefPubMedGoogle Scholar
  • 37 Pareti FI, Niiya K, McPherson JM, Ruggeri ZM. Isolation and characterization of two domains of human von Willebrand factor that interact with fibrillar collagen Types I and III. J Biol Chem 1987; 262: 13835-13841
    PubMedGoogle Scholar
  • 38 Mohri H, Yoshioka A, Zimmerman TS, Ruggeri ZM. Isolation of the von Willebrand factor domain interacting with platelet glycoprotein lb, heparin, and collagen, and characterization of its three distinct functional sites. J Biol Chem 1989; 264: 17361-17367
    PubMedGoogle Scholar
  • 39 Fretto LJ, Fowler WE, McCaslin DR, Erickson HP, McKee PA. Substructure of human von Willebrand factor. Proteolysis by V8 and characterization of two functional domains. J Biol Chem 1986; 261: 15679-15689
    PubMedGoogle Scholar
  • 40 Roberts DD, Williams SB, Gralnick HR, Ginsburg V. Von Willebrand factor binds specifically to sulfated glycolipids. J Biol Chem 1986; 261: 3306-3309
    PubMedGoogle Scholar
  • 41 Christophe O, Obert B, Meyer D, Girma J-P. The binding domain of von Willebrand factor to sulfatides is distinct from those interacting with glycoprotein lb, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673. Blood 1991; 78: 2310-2317
    PubMedGoogle Scholar
  • 42 Sugimoto M, Mohri H, McClintock RA, Ruggeri ZM. Identification of discontinuous von Willebrand factor sequences involved in complex formation with Botrocetin: a model for the regulation of von Willebrand factor binding to platelet glycoprotein lb. J Biol Chem 1991; 266: 18172-18178
    PubMedGoogle Scholar
  • 43 Randi AM, Rabinowitz I, Mancuso DJ, Mannucci PM, Sadler JE. Molecular basis of von Willebrand disease type IIB. Candidate mutations cluster in one disulfide loop between proposed platelet glycoproteins lb binding sequences. J Clin Invest 1991; 87: 1220-1226
    CrossrefPubMedGoogle Scholar
  • 44 Cooney KA, Nichols WC, Bruck ME, Bahou WF, Shapiro AD, Bowie EJW, Gralnick HR, Ginsburg D. The molecular defect in type IIB von Willebrand disease. Identification of four potential missense mutations within the putative GPIb binding domain. J Clin Invest 1991; 87: 1227-1233
    CrossrefPubMedGoogle Scholar
  • 45 Ribba AS, Lavergne JM, Bahnak BR, Derlon A, Pietu G, Meyer D. Duplication of a methionine within the glycoprotein lb binding domain of von Willebrand factor detected by denaturing gradient gel electrophoresis in a patient with type lib von Willebrand disease. Blood 1991; 78: 1738-1743
    PubMedGoogle Scholar
  • 46 Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and Factor VUI/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med 1980; 302: 1047-1051
    CrossrefPubMedGoogle Scholar
  • 47 Mohri H, Fujimura Y, Shima M, Yoshioka A, Houghten RA, Ruggeri ZM, Zimmerman TS. Structure of the von Willebrand factor domain interacting with glycoprotein lb. J Biol Chem 1988; 263: 17901-17904
    PubMedGoogle Scholar
  • 48 Cisse-Thiam M, Perreault P, Chenu J, Girma JP, Meyer D, Drouet L. Peptide 692-708 derived from the GPIb-binding domain of von Willebrand factor is a potent inhibitor of in vivo thrombosis in the guinea pig. Thromb Haemostas 1991; 65: 1180 (Abstr)
    PubMedGoogle Scholar
  • 49 Bemdt MC, Booth WJ, Andrews RK, Castaldi PA. Definition of von Willebrand factor (VWF)-GP Ib-IX complex interaction using vWF-based peptides. Thromb Haemostas 1991; 65: 748 (Abstr)
    PubMedGoogle Scholar
  • 50 Sugimoto M, Ricca G, Hrinda ME, Schreiber AB, Searfoss GH, Bottini E, Ruggeri ZM. Functional modulation of the isolated glycoprotein lb binding domain of von Willebrand factor expressed in Escherichia coli . Biochemistry 1991; 30: 5202-5209
    CrossrefPubMedGoogle Scholar
  • 51 Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science 1987; 238: 491-497
    CrossrefPubMedGoogle Scholar
  • 52 Berliner S, Niiya K, Roberts JR, Houghten RA, Ruggeri ZM. Generation and characterization of peptide-specific antibodies that inhibit von Willebrand factor binding to GP IIb-IIIa without interacting with other adhesive molecules: selectivity is conferred by Pro 1743 and other amino acid residues adjacent to the sequence Argl744-Gly1745-Asp1746. J Biol Chem 1988; 263: 7500-7505
    PubMedGoogle Scholar
  • 53 Foster PA, Fulcher CA, Marti T, Titani K, Zimmerman TS. A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. J Biol Chem 1987; 262: 8443-8446
    PubMedGoogle Scholar
  • 54 Bahou WF, Ginsburg D, Sikkink R, Litwiller R, Fass DN. A monoclonal antibody to von Willebrand factor (vWF) inhibits factor VIII binding. Localization of its antigenic determinant to a nonadecapeptide at the amino terminus of the mature vWF polypeptide. J Clin Invest 1991; 84: 56-61
    PubMedGoogle Scholar
  • 55 Tuley EA, Gaucher C, Jorieux S, Worrall NK, Sadler JE, Mazurier C. Expression of von Willebrand factor “Normandy”: An autosomal mutation that mimics hemophilia A. Proc Natl Acad Sci USA 1991; 88: 6377-6381
    CrossrefPubMedGoogle Scholar
  • 56 Gaucher C, Mercier B, Jorieux S, Oufkir D, Mazurier C. Identification of two point mutations in the von Willebrand factor gene of three families with the “Normandy” variant of von Willebrand disease. Br J Haematol 1991; 78: 506-514
    CrossrefPubMedGoogle Scholar
  • 57 Cacheris PM, Nichols WC, Ginsburg D. Molecular characterization of a unique von Willebrand disease variant. J Biol Chem 1991; 266: 13499-13502
    PubMedGoogle Scholar
  • 58 Kroner PA, Friedman KD, Fahst SA, Scott JP, Montgomery RR. Abnormal binding of Factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. J Biol Chem 1991; 266: 19146-19149
    PubMedGoogle Scholar
  • 59 Nichols TC, Bellinger DA, Reddick RL, Read MS, Koch GG, Brinkhous KM, Griggs TR. Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs. Circulation 1991; 83: 56-64
    PubMedGoogle Scholar
  • 60 Lynch DC, Zimmerman TS, Ruggeri ZM. Von Willebrand factor now cloned. Br J Haematol 1986; 64: 15-20
    CrossrefPubMedGoogle Scholar
  • 61 Dent JA, Galbusera M, Ruggeri ZM. Heterogeneity of plasma von Willebrand factor multimers resulting from proteolysis of the constituent subunit. J Clin Invest 1991; 88: 774-782
    CrossrefPubMedGoogle Scholar