Design of a 20-Amino Acid, Three-Stranded β-Sheet Protein

Abstract

A 20-residue protein (named Betanova) forming a monomeric, three-stranded, antiparallel β sheet was designed using a structural backbone template and an iterative hierarchical approach. Structural and physicochemical characterization show that the β-sheet conformation is stabilized by specific tertiary interactions and that the protein exhibits a cooperative two-state folding-unfolding transition, which is a hallmark of natural proteins. The Betanova molecule constitutes a tractable model system to aid in the understanding of β-sheet formation, including β-sheet aggregation and amyloid fibril formation.