Fig. 6

Localization of the mutations impairing binding of inhibitory mAbs on the DBL1 domain on the DBL1α1-VarO structure. a, b Superposition of the DBL1-VarO crystal structures from the intact and cleaved domains (PDB entry codes 2yk0 and 2xu0, respectively), shown in ribbon representation. The intact domain is shown in brown and the cleaved domain is shown in grey. The region undergoing the conformational change (from residues T51 to K95) is shown in red for the intact domain and in blue for the cleaved domain; only 16 of the 45 residues comprising this segment could be traced in the cleaved domain. This region forms one side of the binding sites for the blood group glycans that were predicted by docking calculations. The A and B blood group trisaccharides are shown as molecular surface representations in yellow and green, respectively. a is viewed from above the glycan binding site and b is rotated by 90° about a vertical axis. c, d. Positions of point mutations in the intact DBL1-VarO (PDB entry code 2yk0) that affect the binding of mAbs, showing the docked blood group trisaccharides, as in views (a, b). The structure is shown as a semi-transparent molecular surface with the ribbon representation. Mutations of the Mut2 protein are in blue and those of Mut4 are in purple. (Mutated residue K87, which is common to Mut2 and Mut4 is not shown as this does not affect the binding of either the mAbs or the blood group glycans; see text and Table 3). The region implicated in the conformational change upon cleavage is shown in red and the side chain of residue R69, shown as spherical atoms, is cyan. c is viewed from above the glycan binding site and d is rotated by 90° about a vertical axis