Selection of Secondary Structures of Heterotypic Supramolecular Peptide Assemblies by an Enzymatic Reaction.

In a model study to investigate the consequence of reactions of intrinsically disordered regions (IDRs) of proteins in the context of the formation of highly ordered structures, we found that enzymatic reactions control the secondary structures of peptides during assembly. Specifically, phosphorylation of an α-helix-dominant peptide results in mostly disordered conformations, which become β-strand-dominant after enzymatic dephosphorylation to regenerate the peptide. In the presence of another peptide largely with a β-strand conformation, direct coassembly of the peptides results in amorphous aggregates consisting of α-helix and β-strand peptides, but the enzymatically generated peptide coassemblies (from the phosphopeptide) mainly adopt a β-strand conformation and form ordered structures (e.g., nanofibers). These results indicate that enzymatic dephosphorylation instructs conformationally flexible peptides to adopt thermodynamically favorable conformations in homotypic or heterotypic supramolecular assemblies.