Proteins carry out many extremely efficient functions, including catalysis and biomolecule recognition. Underlying this efficiency is their extraordinary complexity and ability to fold into unique three-dimensional structures. Attempts to replicate this efficiency through de novo design have only shown moderate success, and it is unclear how modern-day proteins may have evolved. However, short peptides that alternate hydrophobic and hydrophilic residues can self-assemble into amyloid fibrils to achieve well-defined secondary structure. These aggregates may have served as a template from which the first proteins were derived. We designed self-assembling seven-residue peptides that are able to act as Zn2+-dependent esterases. Zn2+ acts to both help induce fibril formation and to serve as a metal cofactor to catalyze acyl ester hydrolysis. Furthermore, we developed a second set of peptides to recognize a target molecule with moderate specificity. The ability of this simple system to catalyze a chemical reaction and exhibit biomolecule recognition suggests that similar peptide aggregates may have been evolutionary precursors to modern-day proteins. Additionally, the ability to use a minimalistic design approach to generate functional fibrils could have implications for the development of simple nanostructured biomaterials. By using an alternating hydrophobic/hydrophilic template, novel functionality can be introduced into simple peptide aggregates.
