Shear stress–induced unfolding of VWF exposes buried, oxidation-sensitive methionine residues. Indicated are methionine residues in the A1 (M1303, M1304, M1385), A2 (M1495, M1521, M1606), and A3 (M1761, M1860) domains of VWF that are susceptible to oxidation. Except for M1495, their conversion into methionine sulfoxide proceeds much more efficient following shear stress–induced unfolding of the molecule, as they are buried in the coiled VWF conformation. Methionine oxidation results in enhanced platelet binding and reduced ADAMTS13-mediated proteolysis.¹