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. Gill; C. 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

doi:10.1182/blood-2014-11-610824

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

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75 Scopus citations

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 language	English (US)
Pages (from-to)	2297-2304
Number of pages	8
Journal	Blood
Volume	125
Issue number	14
DOIs	https://doi.org/10.1182/blood-2014-11-610824
State	Published - Apr 2 2015

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Flood, V. H., Schlauderaff, A. C., Haberichter, S. L., Slobodianuk, T. L., Jacobi, P. M., Bellissimo, D. B., Christopherson, P. A., Friedman, K. D., Gill, J. C., Hoffmann, R. G., Montgomery, R. R., Abshire, T., Dunn, A., Bennett, C., Lusher, J., Rajpurkar, M., Brown, D., Shapiro, A., Lentz, S., ... 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

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

@article{6a90c47ff8c5481e8b8895877597056f,

title = "Crucial role for the VWF A1 domain in binding to type IV collagen",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2015 by The American Society of Hematology.",

year = "2015",

month = apr,

day = "2",

doi = "10.1182/blood-2014-11-610824",

language = "English (US)",

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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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DO - 10.1182/blood-2014-11-610824

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C2 - 25662333

AN - SCOPUS:84926664083

SN - 0006-4971

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SP - 2297

EP - 2304

JO - Blood

JF - Blood

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ER -

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

Abstract

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