Structure and Function of von Willebrand Factor
Thrombosis and HaemostasisPublished 1 January 1999
Zaverio M. Ruggeri
Citations331
SJR quartileQ1
SJR score1.44
SNIP1.14
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TL;DR
A concise summary of established notions on the structure and function of von Willebrand factor is found, followed by a brief discussion of selected recent advances that illustrate how this molecule supports platelet function in hemostasis and thrombosis.
Abstract
Introduction The reader will find here a concise summary of established notions on the structure and function of von Willebrand factor (vWF), followed by a brief discussion of selected recent advances that illustrate how this molecule supports platelet function in hemostasis and thrombosis. A comprehensive review of the topic is beyond the scope of this chapter and may be found elsewhere.1-3
Keywords
Medicine
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The EMBO JournalFull‐length von Willebrand factor (vWF) cDNA encodes a highly repetitive protein considerably larger than the mature vWF subunit.
261 Citations1986C L Verweij, P.J. Diergaarde +2 more
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Journal of Clinical InvestigationSubunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE).
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expression of the mutant with an additional glycine in the D1 domain in AtT-20 cells, a mouse pituitary cell line that can store vWf, led to the storage of the resulting dimers, demonstrating that the mutation did not effect the capacity of the propolypeptide to direct vWF storage while its ability to promote interchain disulfide bonding was eliminated.
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Journal of Biological ChemistryIsolation and characterization of two domains of human von Willebrand factor that interact with fibrillar collagen types I and III.
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BiochemistrycDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms
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199 Citations1985Walter E. Fowler, L J Fretto +3 more
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SciencePropolypeptide of von Willebrand Factor Circulates in Blood and Is Identical to von Willebrand Antigen II
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Journal of Biological ChemistryA heparin-binding domain of human von Willebrand factor. Characterization and localization to a tryptic fragment extending from amino acid residue Val-449 to Lys-728.
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This peptide inhibited both the ristocet in- and botrocetin-mediated binding of vWF to either platelets or purified GP Ib-IX complex (IC50 approximately 50-200 microM) as well as the asialo-vWF- and bovine vWF-dependent agglutination of platelets.
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97 Citations1992Dorothy A. Beacham, Robert J. Wise +2 more
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97 Citations1974Jan A. van Mourik, Bonno N. Bouma +3 more
The results suggest that the intact aggregate is required for factor VIII activity and it is proposed that diminuation of electrostatic repulsion is a factor which contributes to the stability of the aggregates in high ionic strength buffers at neutral pH.
BloodTopology and order of formation of interchain disulfide bonds in von Willebrand factor
95 Citations1987DD Wagner, SO Lawrence +3 more
Recent electron microscopic projections of disulfide bond locations are confirmed and provide support to the hypothetical role of the propolypeptide in the multimerization process of von Willebrand factor.
Journal of Biological Chemistryvon Willebrand factor binds specifically to sulfated glycolipids.
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Journal of Biological ChemistrySubstructure of human von Willebrand factor. Proteolysis by V8 and characterization of two functional domains.
93 Citations1986L J Fretto, Walter E. Fowler +3 more
The effects of Staphylococcus aureus V8 protease (V8) on the multimeric structure of human von Willebrand factor (vWF) were studied to test and expand the model for the substructure of vWF.
Journal of Biological ChemistryGeneration and characterization of peptide-specific antibodies that inhibit von Willebrand factor binding to glycoprotein IIb-IIIa without interacting with other adhesive molecules. Selectivity is conferred by Pro1743 and other amino acid residues adjacent to the sequence Arg1744-Gly1745-Asp1746.
91 Citations1988Shlomo Berliner, K Niiya +3 more
It is demonstrated that peptide-specific antibodies, unlike the promiscuous GP IIb-IIIa receptor, can recognize distinctive structural characteristics of the cell-binding domain of adhesive molecules imposed by residues adjacent to the sequence Arg-Gly-Asp.
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88 Citations1986Masao Hada, M Kaminski +2 more
Results presented here show that plasma von Willebrand factor (vWF) is a substrate for factor XIIIa and can be crosslinked to fibrin during gel formation and can readily form covalent bonds between glutamine in vWF and lysine infibrin alpha chains.
Proceedings of the National Academy of SciencesExpression of von Willebrand factor "Normandy": an autosomal mutation that mimics hemophilia A.
83 Citations1991EA Tuley, Christine Gaucher +4 more
The distinction between hemophilia A and vWD Normandy is clinically important and should be considered in families affected by apparent mild hemophili A that fail to show strict X chromosome-linked inheritance and, particularly, in potential female carriers with low factor VIII levels attributed to extreme lyonization.
Journal of Biological ChemistryAbnormal 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.
81 Citations1991Philip A. Kroner, Kenneth D. Friedman +3 more
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77 Citations1984S Kinoshita, Jillian Harrison +2 more
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Data indicate that (a) the antigenic determinant recognized by W5-6A localizes to a nonadecapeptide at the NH2 terminus of the mature vWF polypeptide, (b) disulfide bonds within vWF9 may be necessary to maintain the structure required for immunoreactivity with W5,6A, and (c) W5 -6A recognizes an immunogenic region on vWF that may be at (or near) the
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70 Citations1987Qingyu Wu, Ludovic Drouet +6 more
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68 Citations1979B.A. Perret, Miha Furlan +1 more
Human factor VIII-related protein isolated from cryoprecipitate by agarose (Sepharose CL-2B) gel filtration concludes that factor VIII aggregates correspond to multimers of a dimeric molecule, i.e. pairs of the basic subunit chain.
Journal of Biological ChemistryMolecular characterization of a unique von Willebrand disease variant. A novel mutation affecting von Willebrand factor/factor VIII interaction
67 Citations1991Phillip Michael Cacheris, WC Nichols +1 more
A critical role for Arg91 in the interaction of vWF with FVIII is suggested and the molecular mechanism for a variant of vWD associated with unusually low FV III levels is identified.
Journal of Cellular PhysiologyExpression of von Willebrand factor in porcine vessels: Heterogeneity at the level of von Willebrand factor mRNA
61 Citations1989Bruce R. Bahnak, Qingyu Wu +7 more
Levels of vWF mRNA and antigen in cultured lung cells were intermediate of those found in the pulmonary artery and aorta and correlated with the estimated number of cells demonstrated to be of endothelial origin in the mixed cell populations grown from the lung.
British Journal of HaematologyIdentification of two point mutations in the von Willebrand factor gene of three families with the ‘Normandy’variant of von Willebrand disease
60 Citations1991Christine Gaucher, Bernard Mercier +3 more
The data show that different mutations may be found in patients with the vWD ‘Normandy’phenotype, and some of them occur within the epitope of monoclonal antibodies inhibiting the vWf/FVIII interaction.
BloodLocalization of factor VIII-procoagulant antigen: an immunohistological survey of the human body using monoclonal antibodies
58 Citations1986Theodorus van der Kwast, HV Stel +3 more
It is tentatively concluded that nonlymphoid cells sporadically present in lymph nodes, in the alveolar septa of lung, and in the red pulp of spleen belong to the mononuclear phagocyte system.
Biochemical JournalPlatelet adhesion to collagen via the α2<i>β</i>1 integrin under arterial flow conditions causes rapid tyrosine phosphorylation of pp125FAK
57 Citations1993Renata Polanowska‐Grabowska, Mark Geanacopoulos +1 more
The results suggest that pp125FAK plays an important role in platelet adhesion to collagen via the alpha 2 beta 1 integrin through the tyrosine kinase inhibitor erbstatin.
Biochemical and Biophysical Research CommunicationsVon Willebrand factor shares a distinctive cysteine-rich domain with thrombospondin and procollagen
56 Citations1987Lois T. Hunt, Winona C. Barker
It is found that a cysteine-rich domain in thrombospondin, also present in types I and III procollagen alpha 1 chains, is related to two internally homologous domains in von Willebrand factor.
BloodThe binding domain of von Willebrand factor to sulfatides is distinct from those interacting with glycoprotein Ib, heparin, and collagen and resides between amino acid residues Leu 512 and Lys 673
54 Citations1991Olivier D. Christophe, Bernadette Obert +2 more
Mapping of this new functional domain of vWF showed that the site interacting with sulfatides is distinct from those involved in binding to platelet glycoprotein Ib, collagen, or heparin, and indicated that the sequence comprising AA 569 to 584 is part of the sulfatide-binding domain or influences its activity.
BloodDDAVP and epinephrine-induced changes in the localization of von Willebrand factor antigen in endothelial cells of human oral mucosa
46 Citations1988M Takeuchi, H Nagura +1 more
A peroxidase-labeled antibody technique revealed von Willebrand factor antigen in rough endoplasmic reticulum, the perinuclear region, and the cytoplasmic vesicles of capillary endothelial cells in oral mucosa and the localization of vWF:Ag was shown to have changed to the basement membrane and the surrounding interstitium.
Biochemical JournalThe role of the 5′-flanking region in the cell-specific transcription of the human von Willebrand factor gene
36 Citations1993V Ferreira, Zahra Assouline +4 more
Results indicate that negative and positive elements in the 5'-flanking region interact to regulate vWF gene expression.
Thrombosis and HaemostasisFine Mapping of Monoclonal Antibody Epitopes on Human von Willebrand Factor Using a Recombinant Peptide Library
20 Citations1992David Ginsburg, Paula Bockenstedt +9 more
A recombinant human von Willebrand factor (vWF) cDNA fragment library was constructed in λgtll for the localization of anti-vWF monoclonal antibody epitopes, suggesting the presence of immuno-dominant epitopes within vWF.
BloodMultimer size dependence of von Willebrand factor binding to crosslinked or noncrosslinked fibrin
19 Citations1990JA Ribes, CW Francis
Findings indicate that vWF released from EC in the presence of fibrin will bind locally, thereby facilitating platelet adhesion to the hemostatic plug or thrombus, and indicates that binding of EC secreted vWF binding tofibrin depends on multimeric size but not on factor XIII crosslinking.
BiochemistryDetermination of the solution structure of a platelet-adhesion peptide of von Willebrand factor
13 Citations1992Heather M. Knott, Michael C. Berndt +3 more
It is proposed that an amphipathic, right-handed alpha-helix in the C-terminal segment of the peptide may be important for the specific molecular interaction of vWF with the GP Ib-IX complex.
Japanese Journal of Thrombosis and HemostasisElectron Microscopy of von Willebrand Factor
11 Citations1991Keizo Ohmori
It is concluded that there was no difference in the size distribution of vWF involved in the ristocetin-induced platelet agglutination, and the numbers of nodules in vWF multimers in each supernatant after various degrees of agglUTination were not different from that of vDF multimers with no aggliltination.
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