Design of a discretely folded mini-protein motif with predominantly β-structure

Here we report the creation of a predominantly beta -structured mini-protein moth. The design target is based on the naturally occurring toxin hand (TH) moths that are composed of four disulfide bonds and three loops that form a 'hand: Analysis and subsequent modification of several generations of mini-proteins produced the final 29-residue mini-protein, The structured moth of this new mini-protein provides insight into the compensatory changes that result in the formation of a tightly packed hydrophobic core in a small, globular beta -structure moth. Additionally, this mini-motif represents a new, distinct surface topology for protein design and a valuable, yet compact, model system for the study of beta -sheet structure in water.