Biopolym. Cell. 2011; 27(4):258-263.
Structural and functional characteristics of vitronectin and its role in haemostasis
1Zhernossekov D. D., 1Zolotareva E. N.
  1. Palladin Institute of Biochemistry, NAS of Ukraine
    9, Leontovycha Str., Kyiv, Ukraine, 01601


Vitronectin is one of the main adhesive proteins circulating in plasma and the component of extracellular matrix. This protein is also present in platelet alpha granules. Structural peculiarities of vitronectin allow it to take part in many processes under normal and pathological states of haemostasis. In plasma, vitronectin circulates as a native monomeric form, but under activation it is transformed into oligomeric form that displays affinity for heparin and forms a stable complex with plasminogen activator inhibitor PAI-1. Oligomeric vitronectin accumulates in atherosclerotic plaques and at sites of vascular injury or inflammation. Recently, new data concerning the functional role of this protein have been obtained. In the present review we have an attempt to summarize the experimental data and clearly define the role of this protein in haemostasis.
Keywords: vitronectin, haemostasis, adhesive proteins


[1] Preissner K. T., Seiffert D. Role of vitronectin and its receptors in haemostasis and vascular remodeling Thromb. Res 1998 89, N 1 P. 1–21.
[2] Tollefsen D. M., Weigel C. J., Kabeer M. H. The presence of methionine or threonine at position 381 in vitronectin is correlated with proteolytic cleavage at arginine 379 J. Biol. Chem 1990 265, N 17 P. 9778–9781.
[3] Boyd N. A., Bradwell A. R., Thompson R. A. Quantitation of vitronectin in serum: evaluation of its usefulness in routine clinical practice J. Clin. Pathol 1993 46, N 11 P. 1042–1045.
[4] Suzuki S., Oldberg A., Hayman E. G., Pierschbacher M. D., Ruoslahti E. Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin EMBO J 1985 4, N 10 P. 2519– 2524.
[5] Ogawa H., Yoneda A., Seno N., Hayashi M., Ishizuka I., Hase S., Matsumoto I. Structures of the N-linked oligosaccharides on human plasma vitronectin Eur. J. Biochem 1995 230, N 3 P. 994–1000.
[6] Ehrlich H. J., Richter B., von der Ahe D., Preissner K. T. Primary structure of vitronectins and homology with other proteins Biology of vitronectins and their receptors / Eds K. T. Preissner, S. Rosenblatt, J. Wegerhoff, C. Kost, D. F. Mosher Amsterdam: Elsevier, 1993 P. 59–66.
[7] Standker L., Enger A., Schulz-Knappe P., Wohn K. D., Germer M., Raida M., Forssmann W. G., Preissner K. T. Structural and functional characterization of vitronectin-derived RGD-containing peptides from human hemofiltrate Eur. J. Biochem 1996 241, N 2 P. 557–563.
[8] Deng G., Royle G., Wang S., Crain K., Loskutoff D. J. Structural and functional analysis of the plasminogen activator inhibitor-1 binding motif in the somatomedin B domain of vitronectin J. Biol. Chem 1996 271, N 22 P. 12716–12723.
[9] Zhou A. Functional structure of the somatomedin B domain of vitronectin Protein Sci 2007 16, N 7 P. 1502–1508.
[10] D'Souza S. E., Ginsberg M. H., Plow E. F. Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif Trends Biochem. Sci 1991 16, N 7 P. 246–250.
[11] de Boer H. C., Preissner K. T., Bouma B. N., de Groot P. G. Binding of vitronectin-thrombin-antithrombin III complex to human endothelial cells is mediated by the heparin binding site of vitronectin J. Biol. Chem 1992 267, N 4 P. 2264–2268.
[12] Izumi M., Shimo-Oka T., Morishita N., Ii I., Hayashi M. Identification of the collagen-binding domain of vitronectin using monoclonal antibodies Cell Struct. Funct 1988 13, N 3 P. 217–225.
[13] Liang O. D., Rosenblatt S., Chhatwal G. S., Preissner K. T. Identification of novel heparin-binding domains in vitronectin FEBS Lett 1997 407, N 2 P. 169–172.
[14] Izumi M., Yamada K. M., Hayashi M. Vitronectin exists in two structurally and functionally distinct forms in human plasma Biochim. Biophys. Acta 1989 990, N 2 P. 101–108.
[15] Tomasini B. R., Owen M. C., Fenton J. W. 2nd, Mosher D. F. Conformational lability of vitronectin: induction of an antigenic change by alpha-thrombin-serpin complexes and by proteolytically modified thrombin Biochemistry 1989 28, N 19 P. 7617–7623.
[16] Yatohgo T., Izumi M., Kashiwagi H., Hayashi M. Novel purification of vitronectin from human plasma by heparin affinity chromatography Cell Struct. Funct 1988 13, N 4 P. 281–292.
[17] Seiffert D. Evidence that conformational changes upon the transition of the native to the modified form of vitronectin are not limited to the heparin binding domain FEBS Lett 1995 368, N 1 P. 155–159.
[18] Stockmann A., Hess S., Declerck P., Timpl R., Preissner K. T. Multimeric vitronectin. Identification and characterization of conformation-dependent self-association of the adhesive protein J. Biol. Chem 1993 268, N 30 P. 22874–22882.
[19] de Boer H. C., de Groot P. G., Bouma B. N., Preissner K. T. Ternary vitronectin-thrombin-antithrombin III complexes in human plasma. Detection and mode of association J. Biol. Chem 1993 268, N 2 P. 1279–1283.
[20] Rosenblatt S., Bassuk J. A., Alpers C. E., Sage E. H., Timpl R., Preissner K. T. Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: characterization of the binding of vitronectin to osteonectin (BMP40, SPARC) Biochem. J 1997 324, Pt 1 P. 311–319.
[21] Preissner K. T., Muller-Berghaus G. Neutralization and binding of heparin by S protein/vitronectin in the inhibition of factor Xa by antithrombin III. Involvement of an inducible heparin binding domain of S protein/vitronectin J. Biol. Chem 1987 262, N 25 P. 12247–12253.
[22] Hildebrand A., Preissner K. T., Muller-Berghaus G., Teschemacher H. A novel beta-endorphin binding protein. Complement S protein (vitronectin) exhibits specific non-opioid binding sites for beta-endorphin upon interaction with heparin or surfaces J. Biol. Chem 1989 264, N 26 P. 15429–15434.
[23] Preissner K. T., Grulich-Henn J., Ehrlich H. J., Declerk P., Justus C., Collen D., Pannekoek H., Muller-Berghaus G. Structural requirements for the extracellular interaction of plasminogen activator inhibitor 1 with endothelial cell matrix-associated vitronectin J. Biol. Chem 1990 265, N 30 P. 18490–18498.
[24] Waltz D. A., Chapman H. A. Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy J. Biol. Chem 1994 269, N 20 14746–14750.
[25] Seiffert D., Smith J. W. The cell adhesion domain in plasma vitronectin is cryptic J. Biol. Chem 1997 272, N 21 P. 13705– 13710.
[26] Hynes R. O. Integrins: bidirectional, allosteric signaling machines Cell 2002 110, N 6 P. 673–687.
[27] Bennett J. S. Platelet-fibrinogen interactions Ann. N. Y. Acad. Sci 2001 936 P. 340–354.
[28] Kasirer-Friede A., Kahn M. L., Shattil S. J. Platelet integrins and immunoreceptors Immunol. Rev 2007 218 P. 247–264.
[29] Takagi J. Structural basis for ligand recognition by RGD (ArgGly-Asp)-dependent integrins Biochem. Soc. Trans 2004 32, Pt 3 P. 403–406.
[30] Serini G., Valdembri D., Bussolino F. Integrins and angiogenesis: a sticky business Exp. Cell Res 2006 312, N 5 P. 651–658.
[31] Eliceiri B. P. Integrin and growth factor receptor crosstalk Circ. Res 2001 89, N 12 P. 1104–1110.
[32] Bader B. L., Rayburn H., Crowley D., Hynes R. O. Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha V integrins Cell 1998 95, N 4 P. 507–519.
[33] Brooks P. C., Montgomery A. M., Rosenfeld M., Reisefeld R. A., Hu T., Klier G., Cheresh D. A. Integrin alpha V beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels Cell 1994 79, N 7 P. 1157–1164.
[34] Gutheil J. C., Campbell T. N., Pierce P. R., Watkins J. D., Huse W. D., Bodkin D. J., Cheresh D. A. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphaVbeta3 Clin. Cancer Res 2000 6, N 8 P. 3056–3061.
[35] Roger M., Hogasen K., Solum N. O., Mollnes T. E., Hovig T. Vitronectin inhibits blood platelet aggregation Platelets 1993 4, N 4 P. 225–229.
[36] Reheman A., Gross P., Yang H., Chen P., Allen D., Leytin V., Freedman J., Ni H. Vitronectin stabilizes thrombi and vessel occlusion but plays a dual role in platelet aggregation J. Thromb. Haemost 2005 3, N 5 P. 875–883.
[37] Roka-Moya Y. M., Zhernossekov D. D., Zolotareva E. M., Grinenko T. V. The influence of exogenous Lys-plasminogen on ADP-induced platelet aggregation Bulletin of the University of Kiev, series: Biology 2011 58 P. 34–36.
[38] Christensen K. Platelet activation and inhibition in connection with vascular stents Acta Universitatis Upsaliensis 2007 98 p.
[39] Vogel B. E., Lee S. J., Hildebrand A., Craig W., Pierschbacher M. D., Wong-Staal F., Ruoslahti E. A novel integrin specificity exemplified by binding of the alpha v beta5 integrin to the basic domain of the HIV Tat protein and vitronectin J. Cell Biol 1993 121, N 2 P. 461–468.
[40] Asch E., Podack E. Vitronectin binds to activated human platelets and plays a role in platelet aggregation J. Clin. Invest 1990 85, N 5 P. 1372–1378.
[41] Jarvis G. E., Atkinson B. T., Frampton J., Watson S. P. Thrombin-induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb Br. J. Pharmacol 2003 138, N 4 P. 574–583.
[42] Schvartz I., Seger D., Maik-Rachline G., Kreizman T., Shaltiel S. Truncated vitronectins: binding to immobilized fibrin and to fibrin clots, and their subsequent interaction with cells Biochem. Biophys. Res. Commun 2002 290, N 2 P. 682–689.