Activation by elongational flow of von Willebrand factor (VWF) is critical for primary
hemostasis. Mutations causing type 2B von Willebrand disease (VWD), platelet-type VWD
(PT-VWD), and tensile force each increase affinity of the VWF A1 domain and platelet
glycoprotein Ibα (GPIbα) for one another; however, the structural basis for these
observations remains elusive. Directed evolution was used to discover a further gain-of-
function mutation in A1 that shifts the long range disulfide bond by one residue. We solved …