Positions of the architecture switching substitutions. The original (top) and redesigned interface (bottom) sequences in DpHF18 and DpHF19 are modelled on both backbone structures. The five substitutions introduced during refinement are shown as thicker sticks, and the relevant surrounding residues as thinner lines. The unintended helix packing in the DpHF18 structure is disfavoured in the redesign by substituting a valine residue and a leucine residue (shown in Supplementary Fig. 3 ) for aspartates (left column). Three additional substitutions introduce hydrogen bond networks across the desired interface (right column).
