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-ΔCC, residues 1473-1668). Compared with A2-ΔCC, 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-ΔCC. 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. © 2010 by The American Society of Hematology.
CITATION STYLE
Luken, B. M., Winn, L. Y. N., Emsley, J., Lane, D. A., & Crawley, J. T. B. (2010). The importance of vicinal cysteines, C1669 and C1670, for von Willebrand factor A2 domain function. Blood, 115(23), 4910–4913. https://doi.org/10.1182/blood-2009-12-257949
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