Catalytically Active Amyloids as Future Bionanomaterials

Abstract

Peptides and proteins can aggregate into highly ordered and structured conformations called amyloids. These supramolecular structures generally have convergent features, such as the formation of intermolecular beta sheets, that lead to fibrillary architectures. The resulting fibrils have unique mechanical properties that can be exploited to develop novel nanomaterials. In recent years, sequences of small peptides have been rationally designed to self-assemble into amyloids that catalyze several chemical reactions. These amyloids exhibit reactive surfaces that can mimic the active sites of enzymes. In this review, I provide a state-of-the-art summary of the development of catalytically active amyloids. I will focus especially on catalytic activities mediated by hydrolysis, which are the most studied examples to date, as well as novel types of recently reported activities that promise to expand the possible repertoires. The combination of mechanical properties with catalytic activity in an amyloid scaffold has great potential for the development of future bionanomaterials aimed at specific applications.

Metal Ions Can Modulate the Self-Assembly and Activity of Catalytic Peptide Amyloids

“…The unique conformational architecture of amyloids has fueled interest to design novel amyloid-based nanomaterials . Amyloids can self-assemble from very small to large polypeptides, are chemically stable, and exhibit unique mechanical properties, which are highly attractive features to design novel nanomaterials. − In recent years, the development of amyloids with catalytic activity has raised their attractiveness for application purposes .…”

“…Based on the histidine-rich active site of carbonic anhydrase (CA), Rufo et al reported the first set of peptides to self-assemble in vitro into amyloids that become catalytically active when bound to zinc. , The amyloids cleaved ester bonds similar to CA. Peptide IHIHIQI was the most active sequence and has served as template to develop many other catalytic amyloids. ,,− Amyloid activities include hydrolysis of ester and phosphoester bonds, redox reactions, and retro aldol condensations, among others. , Based on the active site of nucleotide-processing enzymes, we have developed catalytic amyloids carrying active aspartate groups (Asp). , These catalytic amyloids exhibit manganese-dependent hydrolytic activity that specifically cleaves the phosphoanhydride bonds of adenosine triphosphate (ATP) and other nucleotides. Most catalytic amyloids rely on metal ions for their activity. , It is known that divalent metals can influence the aggregation of different (noncatalytic) pathological amyloids. − Herein, we show that biologically relevant metal ions can guide the assembly of a small peptide into metal-specific aggregation kinetics and morphologies.…”

Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes

“…It has been hypothesized that the earliest enzymes on Earth might have arisen from the spontaneous self-assembly of short peptides to form supramolecular structures. − Specifically, it has been suggested that amyloids may have acted as the scaffold supporting primitive catalytic activities. , As amyloids use amino acid sequences as their building blocks, and their assembly is driven and sustained by noncovalent interactions, they share similarities with natural proteins . In favor of this hypothesis, several artificial amyloids formed by short, and often repetitive, amino acid sequences have been shown to act as enzyme mimetics. − Although, in general terms, they are catalytically less efficient than modern enzymes, the modularity, flexible design, stability, and reusability of these nanozymes endow them with advantages, , relative to their natural counterparts, including lower synthesis and modification costs.…”

Nanomechanical properties of SSTSAA microcrystals are dominated by the inter-sheet packing

“…Functional amyloids have been found to be involved in, for instance, natural adhesives, plant seed maturation, bacterial biofilm formation and hormone storage [2][3][4][5]. Moreover, it is now clear that we can exploit them technologically in a wide range of applications [6][7][8]. Not unlike the way collagen-derived polypeptides are used in bio-engineering to produce aerogels (to serve as haemostatic sponges, for example) or hydrogels [9,10].…”