Figure 3
The structures of the Mcl-1–scFv and Mcl-1–Fab complexes. Mcl-1 is bound by the scFv (PDB entry 6qb3) or Fab (PDB entry 6qb6) via the BH2 helix. (a) Models of Mcl-1–scFv and Mcl-1–Fab overlaid. The epitope in the C-terminal region is shown in orange. The VH and VL regions of the Fab are structurally very similar to those in the scFv, suggesting that the addition of the constant domains had little effect on the binding mode. For reference, a natural Bim BH3 peptide ligand (blue) is overlaid (PDB entry 2pqk; Fire et al., 2010). (b) Residues from the epitope interaction are annotated and shown in orange stick representation. Arg310 is in an extended conformation and is buried in the scFv CDR binding site. (c–f) Stick representations of the main interactions between Mcl-1 (orange) and scFv/Fab (grey). Water atoms are shown as red spheres. |