DESIGN OF A MONOMERIC 23-RESIDUE POLYPEPTIDE WITH DEFINED TERTIARY STRUCTURE

Small proteins or protein domains generally require disulfide bridges or metal sites for their stabilization. Here it is shown that the beta beta alpha architecture of zinc fingers can be reproduced in a 23-res idue polypeptide in the absence of metal ions. The sequence was obtain ed through an iterative design process. A key feature of the final des ign is the incorporation of a type II' beta turn to aid in beta-hairpi n formation. Nuclear magnetic resonance analysis reveals that the alph a helix and beta hairpin are held together by a defined hydrophobic co re. The availability of this structural template has implications for the development of functional polypeptides.