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Eur J Biochem. 1991 Mar 14;196(2):369-75.

Effect of deletion of the A1 domain of von Willebrand factor on its binding to heparin, collagen and platelets in the presence of ristocetin.

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Department of Haematology, University Hospital Utrecht, The Netherlands.


In order to study the functional importance of the collagen, heparin and glycoprotein-Ib-binding domain, we deleted the A1 domain of von Willebrand factor (vWF), corresponding to residues 478-716, by oligonucleotide-directed mutagenesis. The resulting delta A1-vWF cDNA was expressed in COS-1 monkey kidney cells and compared to wild-type vWF. The higher-molecular-mass multimers were decreased in delta A1 recombinant von Willebrand factor (delta A1-rvWF) compared to plasma vWF and rvWF. The reactivity of delta A1-rvWF and rvWF with monoclonal antibodies directed against the collagen-binding domain (residues 969-992), the vessel-wall-binding domain, and the binding site for glycoprotein IIb-IIIa on platelets was identical. The interaction with vWF of the monoclonal antibody directed against the glycoprotein Ib binding domain was abolished for delta A1-rvWF, and similar to plasma vWF for rvWF. The binding of factor VIII to delta A1-rvWF and rvWF was similar. delta A1-rvWF and rvWF bound similarly to collagen, but the binding of delta A1-rvWF to heparin and to platelets in the presence of ristocetin were abolished. These data indicate that the heparin-binding site in the A1 domain is essential. There is no second binding domain for glycoprotein Ib outside the A1 domain. The collagen-binding domain in the A1 domain is either not active or its action can be compensated by the second collagen-binding domain.

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