Crucial role for the VWF A1 domain in binding to type IV collagen

Veronica H. Flood, Abraham C. Schlauderaff, Sandra L. Haberichter, Tricia L. Slobodianuk, Paula M. Jacobi, Daniel B. Bellissimo, Pamela A. Christopherson, Kenneth D. Friedman, Joan Cox Gill, Raymond G. Hoffmann, Robert R. Montgomery, T. Abshire, A. Dunn, C. Bennett, J. Lusher, M. Rajpurkar, D. Brown, A. Shapiro, S. Lentz, J. GillC. Leissinger, M. Ragni, J. Hord, M. Manco-Johnson, J. Strouse, A. Ma, L. Valentino, L. Boggio, A. Sharathkumar, R. Gruppo, B. Kerlin, J. Journeycake, R. Kulkarni, D. Green, D. Mahoney, L. Mathias, A. Bedros, C. Diamond, A. Neff, D. Di Michele, P. Giardina, A. Cohen, M. Paidas, E. Werner, A. Matsunaga, M. Tarantino, F. Shafer, B. Konkle, A. Cuker, P. Kouides, D. Stein

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed.We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain.We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis.

Original languageEnglish (US)
Pages (from-to)2297-2304
Number of pages8
JournalBlood
Volume125
Issue number14
DOIs
StatePublished - Apr 2 2015

Fingerprint

Collagen Type IV
von Willebrand Factor
Collagen
Platelets
Blood Platelets
Type 1 von Willebrand Disease
Type 2 von Willebrand Disease
von Willebrand Diseases
Mutagenesis
Site-Directed Mutagenesis
Hemostasis
Blood Vessels
Healthy Volunteers

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Flood, V. H., Schlauderaff, A. C., Haberichter, S. L., Slobodianuk, T. L., Jacobi, P. M., Bellissimo, D. B., ... Stein, D. (2015). Crucial role for the VWF A1 domain in binding to type IV collagen. Blood, 125(14), 2297-2304. https://doi.org/10.1182/blood-2014-11-610824

Crucial role for the VWF A1 domain in binding to type IV collagen. / Flood, Veronica H.; Schlauderaff, Abraham C.; Haberichter, Sandra L.; Slobodianuk, Tricia L.; Jacobi, Paula M.; Bellissimo, Daniel B.; Christopherson, Pamela A.; Friedman, Kenneth D.; Gill, Joan Cox; Hoffmann, Raymond G.; Montgomery, Robert R.; Abshire, T.; Dunn, A.; Bennett, C.; Lusher, J.; Rajpurkar, M.; Brown, D.; Shapiro, A.; Lentz, S.; Gill, J.; Leissinger, C.; Ragni, M.; Hord, J.; Manco-Johnson, M.; Strouse, J.; Ma, A.; Valentino, L.; Boggio, L.; Sharathkumar, A.; Gruppo, R.; Kerlin, B.; Journeycake, J.; Kulkarni, R.; Green, D.; Mahoney, D.; Mathias, L.; Bedros, A.; Diamond, C.; Neff, A.; Di Michele, D.; Giardina, P.; Cohen, A.; Paidas, M.; Werner, E.; Matsunaga, A.; Tarantino, M.; Shafer, F.; Konkle, B.; Cuker, A.; Kouides, P.; Stein, D.

In: Blood, Vol. 125, No. 14, 02.04.2015, p. 2297-2304.

Research output: Contribution to journalArticle

Flood, VH, Schlauderaff, AC, Haberichter, SL, Slobodianuk, TL, Jacobi, PM, Bellissimo, DB, Christopherson, PA, Friedman, KD, Gill, JC, Hoffmann, RG, Montgomery, RR, Abshire, T, Dunn, A, Bennett, C, Lusher, J, Rajpurkar, M, Brown, D, Shapiro, A, Lentz, S, Gill, J, Leissinger, C, Ragni, M, Hord, J, Manco-Johnson, M, Strouse, J, Ma, A, Valentino, L, Boggio, L, Sharathkumar, A, Gruppo, R, Kerlin, B, Journeycake, J, Kulkarni, R, Green, D, Mahoney, D, Mathias, L, Bedros, A, Diamond, C, Neff, A, Di Michele, D, Giardina, P, Cohen, A, Paidas, M, Werner, E, Matsunaga, A, Tarantino, M, Shafer, F, Konkle, B, Cuker, A, Kouides, P & Stein, D 2015, 'Crucial role for the VWF A1 domain in binding to type IV collagen', Blood, vol. 125, no. 14, pp. 2297-2304. https://doi.org/10.1182/blood-2014-11-610824
Flood VH, Schlauderaff AC, Haberichter SL, Slobodianuk TL, Jacobi PM, Bellissimo DB et al. Crucial role for the VWF A1 domain in binding to type IV collagen. Blood. 2015 Apr 2;125(14):2297-2304. https://doi.org/10.1182/blood-2014-11-610824
Flood, Veronica H. ; Schlauderaff, Abraham C. ; Haberichter, Sandra L. ; Slobodianuk, Tricia L. ; Jacobi, Paula M. ; Bellissimo, Daniel B. ; Christopherson, Pamela A. ; Friedman, Kenneth D. ; Gill, Joan Cox ; Hoffmann, Raymond G. ; Montgomery, Robert R. ; Abshire, T. ; Dunn, A. ; Bennett, C. ; Lusher, J. ; Rajpurkar, M. ; Brown, D. ; Shapiro, A. ; Lentz, S. ; Gill, J. ; Leissinger, C. ; Ragni, M. ; Hord, J. ; Manco-Johnson, M. ; Strouse, J. ; Ma, A. ; Valentino, L. ; Boggio, L. ; Sharathkumar, A. ; Gruppo, R. ; Kerlin, B. ; Journeycake, J. ; Kulkarni, R. ; Green, D. ; Mahoney, D. ; Mathias, L. ; Bedros, A. ; Diamond, C. ; Neff, A. ; Di Michele, D. ; Giardina, P. ; Cohen, A. ; Paidas, M. ; Werner, E. ; Matsunaga, A. ; Tarantino, M. ; Shafer, F. ; Konkle, B. ; Cuker, A. ; Kouides, P. ; Stein, D. / Crucial role for the VWF A1 domain in binding to type IV collagen. In: Blood. 2015 ; Vol. 125, No. 14. pp. 2297-2304.
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abstract = "Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed.We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain.We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis.",
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T1 - Crucial role for the VWF A1 domain in binding to type IV collagen

AU - Flood, Veronica H.

AU - Schlauderaff, Abraham C.

AU - Haberichter, Sandra L.

AU - Slobodianuk, Tricia L.

AU - Jacobi, Paula M.

AU - Bellissimo, Daniel B.

AU - Christopherson, Pamela A.

AU - Friedman, Kenneth D.

AU - Gill, Joan Cox

AU - Hoffmann, Raymond G.

AU - Montgomery, Robert R.

AU - Abshire, T.

AU - Dunn, A.

AU - Bennett, C.

AU - Lusher, J.

AU - Rajpurkar, M.

AU - Brown, D.

AU - Shapiro, A.

AU - Lentz, S.

AU - Gill, J.

AU - Leissinger, C.

AU - Ragni, M.

AU - Hord, J.

AU - Manco-Johnson, M.

AU - Strouse, J.

AU - Ma, A.

AU - Valentino, L.

AU - Boggio, L.

AU - Sharathkumar, A.

AU - Gruppo, R.

AU - Kerlin, B.

AU - Journeycake, J.

AU - Kulkarni, R.

AU - Green, D.

AU - Mahoney, D.

AU - Mathias, L.

AU - Bedros, A.

AU - Diamond, C.

AU - Neff, A.

AU - Di Michele, D.

AU - Giardina, P.

AU - Cohen, A.

AU - Paidas, M.

AU - Werner, E.

AU - Matsunaga, A.

AU - Tarantino, M.

AU - Shafer, F.

AU - Konkle, B.

AU - Cuker, A.

AU - Kouides, P.

AU - Stein, D.

PY - 2015/4/2

Y1 - 2015/4/2

N2 - Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed.We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain.We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis.

AB - Von Willebrand factor (VWF) contains binding sites for platelets and for vascular collagens to facilitate clot formation at sites of injury. Although previous work has shown that VWF can bind type IV collagen (collagen 4), little characterization of this interaction has been performed.We examined the binding of VWF to collagen 4 in vitro and extended this characterization to a murine model of defective VWF-collagen 4 interactions. The interactions of VWF and collagen 4 were further studied using plasma samples from a large study of both healthy controls and subjects with different types of von Willebrand disease (VWD). Our results show that collagen 4 appears to bind VWF exclusively via the VWF A1 domain, and that specific sequence variations identified through VWF patient samples and through site-directed mutagenesis in the VWF A1 domain can decrease or abrogate this interaction. In addition, VWF-dependent platelet binding to collagen 4 under flow conditions requires an intact VWF A1 domain.We observed that decreased binding to collagen 4 was associated with select VWF A1 domain sequence variations in type 1 and type 2M VWD. This suggests an additional mechanism through which VWF variants may alter hemostasis.

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