Evolution of a protein fold in vitro

A "switch" mutant of the Arc repressor homodimer was constructed by interch anging the sequence positions of a hydrophobic core residue, Leucine 12, an d an adjacent surface polar residue, asparagine 11, in each strand of an in tersubunit beta sheet. The mutant protein adopts a fold in which each beta strand is replaced by a right-handed helix and side chains in this region u ndergo significant repacking, The observed structural changes allow the pro tein to maintain solvent exposure of polar side chains and optimal burial o f hydrophobic side chains. These results suggest that new protein folds can evolve from existing folds without drastic or large-scale mutagenesis.