A CONVERGENT APPROACH TO PROTEIN DESIGN - METAL ION-ASSISTED SPONTANEOUS SELF-ASSEMBLY OF A POLYPEPTIDE INTO A TRIPLE-HELIX BUNDLE PROTEIN

A novel metal ion-assisted self-organizing molecular process is described by which a small peptide has been assembled into a large and topologically predetermined protein tertiary structure. The intrinsic binding energy of a metal ion coordination complex as well as the stringent geometrical requirements present for a strong metal ion-ligand interaction has been exploited to control the oligomeric state as well as the relative orientation of peptide subunits participating in an intermolecular assembly process. A 15-residue amphiphilic peptide with a 2,2'-bipyridine functionality at the N-terminus was designed and shown to undergo spontaneous self-assembly, in the presence of transition metal ions, to form a 45-residue triple-helical coiled-coil metalloprotein.