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Updated: Jun 14, 2026

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
The importance of vicinal cysteines, C1669 and C1670, for von Willebrand factor A2 domain function
Brenda M Luken1, Luke Y N Winn, Jonas Emsley
1Department of Haematology, Imperial College London, London, UK. b.luken@imperial.ac.uk
Abstract:
The von Willebrand factor (VWF) A2 crystal structure has revealed the presence of a rare vicinal disulfide bond between C1669 and C1670, predicted to influence domain unfolding required for proteolysis by ADAMTS13. We prepared VWF A2 domain fragments with (A2-VicCC, residues 1473-1670) and without the vicinal disulfide bond (A2-DeltaCC, residues 1473-1668). Compared with A2-DeltaCC, A2-VicCC exhibited impaired proteolysis and also reduced binding to ADAMTS13. Circular dichroism studies revealed that A2-VicCC was more resistant to thermal unfolding than A2-DeltaCC. Mutagenesis of C1669/C1670 in full-length VWF resulted in markedly increased susceptibility to cleavage by ADAMTS13, confirming the important role of the paired vicinal cysteines in VWF A2 domain stabilization.
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