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⇱ Structure of pre-pro-von Willebrand factor and its expression in heterologous cells | Nature

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Abstract

Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation. Native vWF is a disulphide-bonded homopolymer; the monomeric subunits, of apparent relative molecular mass (Mr) 220,000 (220K) are derived from an intracellular precursor estimated at 260–275K (refs 1–5). Multimer assembly is preceded by the formation of dimers, linked near their C-termini, which then assemble into filamentous polymers. The importance of the removal of the large vWF pro-polypeptide during multimer assembly, and whether this or other stages of the complex post-translational processing require components specific to endothelial cells or megakaryocytes, is unknown. Here we report an analysis of the complete sequence of pre-pro-vWF and expression of the molecule in heterologous cells. The vWF precursor is composed of several repeated subdomains. When expressed in COS and CHO cells, it is cleaved and assembled into biologically active high relative molecular mass disulphide bonded multimers. This suggests that the information for assembly of this complex molecule resides largely within its primary structure.

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Author information

Author notes

  1. David Ginsburg

    Present address: Howard Hughes Medical Institute, 1150 West Campus Drive, Ann Arbor, Michigan, 48109, USA

Authors and Affiliations

  1. Division of Hematology/Oncology, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    David T. Bonthron, David Ginsburg & Stuart H. Orkin

  2. the Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, 02115, USA

    David T. Bonthron, David Ginsburg & Stuart H. Orkin

  3. Howard Hughes Medical Institute and the Departments of Medicine and Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts, 02115, USA

    David T. Bonthron & Stuart H. Orkin

  4. Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Robert I. Handin, Bruce Ewenstein, Joseph Loscalzo & David Ginsburg

  5. Genetics Institute, 87 Cambridge Park Drive, Cambridge, Massachusetts, USA

    Randal J. Kaufman, Louise C. Wasley, Elizabeth C. Orr & Lisa M. Mitsock

Authors
  1. David T. Bonthron
  2. Robert I. Handin
  3. Randal J. Kaufman
  4. Louise C. Wasley
  5. Elizabeth C. Orr
  6. Lisa M. Mitsock
  7. Bruce Ewenstein
  8. Joseph Loscalzo
  9. David Ginsburg
  10. Stuart H. Orkin

About this article

Cite this article

Bonthron, D., Handin, R., Kaufman, R. et al. Structure of pre-pro-von Willebrand factor and its expression in heterologous cells. Nature 324, 270–273 (1986). https://doi.org/10.1038/324270a0

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  • DOI: https://doi.org/10.1038/324270a0

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