Alpha carbon (Ca) root mean square fluctuations (RMSF) in wt A1-A2 and A1-A2 mutants. (A) Alpha carbon (Ca) RMSF differences between the ones of A1-A2 mutants (p.R1315C, red; p.R1315L, green; p.R1374C, blue; and p.R1374H, yellow) and the ones of wt A1-A2. (B) The largest differences (residues 1345-1355 and residues 1478-1488) are reported on the reference structure of wt A1-A2 alongside the position of mutated residues (lime/orange sticks). The original RMSF values are reported in the supplemental Figure 6. (C) Contacts between A1 and D3 domains of VWF in the context of tubule structure (reference structure: PDB ID 8D3D; the experimental cryogenic electron microscopy data are reported from the RCSB-PDB on the left together with domains). The A1 domain and its residues 1345-1355 are reported in blue, D3 domain and its residues 895-902, 988-999 and 1007-1013 are evidenced in yellow. Residues 344-371 belonging to the VWF (ie, within 0.75 nm of the surfaces of the A1 and D3 domains) without domain assignment are highlighted in brown. Van der Waals surfaces have been used for representing single residues.