Supplementary Figure 7: Structural analysis of C1q-specific Fc variants.
(a) Crystal packing environment for A801-Fc. The crystallographic packing lattice is shown for A801-Fc (PDB ID: 5V43). The dimer from one asymmetric unit is shown in cartoon representation, with Cγ2A in white; Cγ2B in blue; and Cγ3B in pink. Surrounding asymmetric units are shown in ribbon representation (magenta). No contacts or atomic clashes were observed between Cγ2B and molecules from surrounding asymmetric units. (b) B factors distribution fucosylated-WT Fc (PDB ID: 3AVE), G801-Fc (PDB ID: 5V4E), aglycosylated-WT Fc (PDB ID: 3S7G), A801-Fc (PDB ID: 5V43). The coloring of the figure is based on the B factors gradient with lowest (blue) to highest (red). The dash line represents disordered regions. (c) Distance of FcγR-binding motifs of Fc domain to FcγRI (PDB ID: 4X4M). FcγR is shown as a white transparent surface and the secondary structure of the whole complex is shown in ribbon. Two different regions on the Fc are both identified to be important for FcγR and Fc complex formation: LLPP motif (important residue Leu235 is shown in sticks) and C’E loop. (d-e) Overlaid Cγ2 and 'soft' C'E loop of 801-Fc with wild type Fc. (d) Cγ2 of G801-Fc (PDB 5V4E, purple) was superimposed with fucosylated-WT Fc (orange, PDB: 3AVE). (e) G801-Fc (purple) was superimposed with aglycosylated-WT Fc (green, PDB: 3S7G). The 'soft' C'E loop of G801-Fc was highlighted by arrow. The glycan in PDB 3AVE is shown in white.
