Catalytic amyloids

Abstract

Amyloid fibril assemblies of proteins and synthetic peptides exhibit in some instances catalytic activities. Reactions catalyzed by peptide amyloids include hydrolysis, condensation, and redox reactions. In comparison with biological enzymes, catalytic amyloid-like assemblies display lesser selectivity and, in general, lower efficiency. The physiological role of catalytic amyloids may illuminate yet unknown aspects of protein misfolding diseases. Protein amyloids generally constitute β-sheet rich fibrillar assemblies. Amyloid fibrils have been identified in varied diseases, formed by bacterially secreted proteins, and generated in de novo designed peptides. This review article summarizes the burgeoning body of work reporting catalytic properties of amyloid fibrils. We highlight representative studies focusing on catalytic amyloid peptides, both synthetic and naturally occurring. We discuss the structural features associated with catalysis and putative catalytic sites on amyloid fibrils’ surfaces. We also highlight studies demonstrating catalytic functions of short amyloid-like sequences and their possible involvement in early-life reactions, acting as primitive enzymes. Finally, we discuss recent reports of the catalytic activities of native amyloids, pointing to possible roles of amyloid catalysis in disease progression and pathologies. Protein amyloids generally constitute β-sheet rich fibrillar assemblies. Amyloid fibrils have been identified in varied diseases, formed by bacterially secreted proteins, and generated in de novo designed peptides. This review article summarizes the burgeoning body of work reporting catalytic properties of amyloid fibrils. We highlight representative studies focusing on catalytic amyloid peptides, both synthetic and naturally occurring. We discuss the structural features associated with catalysis and putative catalytic sites on amyloid fibrils’ surfaces. We also highlight studies demonstrating catalytic functions of short amyloid-like sequences and their possible involvement in early-life reactions, acting as primitive enzymes. Finally, we discuss recent reports of the catalytic activities of native amyloids, pointing to possible roles of amyloid catalysis in disease progression and pathologies. (Michaelis-Menten constant, KM); in basic enzymology models, the affinity constant represents the propensity of enzyme–substrate complexation to occur and is defined by the concentration of substrate providing half of enzyme maximal activity (half of the highest rate of reaction). an elongated proteinaceous assembly in which the peptides/protein strands are generally stacked perpendicular to the fibril long axis. a region where substrate molecules bind, form transient bonds, and undergo a chemical reaction. In enzymes, active sites consist of residues forming ‘pockets’ that enable specific binding of substrate molecules. In many enzymes, triads constitute the catalytic sites. the ratio of substrate conversion in an active site (also known as the turnover number, Kcat), per affinity constant (Kcat/KM). The catalytic efficiency takes into account the two main factors affecting catalysis: the substrate complexation with the catalyst and the conversion rate to the product.