Removal of the N-linked glycans at N1515 does not enhance clearance in VWF with a structurally constrained A2 domain. (A) To examine a potential role for A2 domain conformation in modulating clearance VWF, a previously described cysteine-clamp mutation (N1493C/C1670S) was inserted into full-length rVWF (rVWF-CC) and VWF-N1515Q (VWF-N1515Q-CC). This mutation creates a structurally constrained A2 due to the presence of a long-range disulfide bridge, homologous to those present in the A1 and A3 domains. (B) Clearance was assessed in VWF^−/− mice. All results are plotted as percentage residual VWF:antigen levels relative to the amount injected. Data are presented as mean ± SEM.