Selective protein-protein interactions driven by a phenylalanine interface

Highly specific protein-protein interfaces have been the subject of considerable study for their potential utility in disrupting or interrogating cellular signaling and control networks. We report that coiled-coil sequences decorated with phenylalanine core residues fold into stable a-helical bundles and that these self-sort from similar peptide assemblies with aliphatic core side chains. For self-assembled ensembles derived from 30-residue monomeric peptides, the Delta G of specificity is -1.5 kcal/mol, comparable with earlier self-sorting coiled-coil systems. Intriguingly, although this interface is constructed from canonical amino acids, it does not appear to have been exploited in native proteins.