Design of a Monomeric 23-Residue Polypeptide with Defined Tertiary Structure

Abstract

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