Conformational activation and inhibition of von Willebrand factor by targeting its autoinhibitory module

Activation of von Willebrand factor (VWF) is a tightly controlled process governed primarily by local elements around its A1 domain. Recent studies suggest that the O-glycosylated sequences flanking the A1 domain constitute a discontinuous and force-sensitive autoinhibitory module (AIM), although its extent and conformation remains controversial. Here, we used a targeted screening strategy to identify two groups of nanobodies. One group, represented by clone 6D12, is conformation-insensitive …