Cargando…

Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes

[Image: see text] Enzymes typically fold into defined 3D protein structures exhibiting a high catalytic efficiency and selectivity. It has been proposed that the earliest enzymes may have arisen from the self-assembly of short peptides into supramolecular amyloid-like structures. Several artificial...

Descripción completa

Detalles Bibliográficos
Autores principales: Navarro, Susanna, Díaz-Caballero, Marta, Peccati, Francesca, Roldán-Martín, Lorena, Sodupe, Mariona, Ventura, Salvador
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510724/
https://www.ncbi.nlm.nih.gov/pubmed/37647583
http://dx.doi.org/10.1021/acsnano.3c04164
_version_ 1785108006305792000
author Navarro, Susanna
Díaz-Caballero, Marta
Peccati, Francesca
Roldán-Martín, Lorena
Sodupe, Mariona
Ventura, Salvador
author_facet Navarro, Susanna
Díaz-Caballero, Marta
Peccati, Francesca
Roldán-Martín, Lorena
Sodupe, Mariona
Ventura, Salvador
author_sort Navarro, Susanna
collection PubMed
description [Image: see text] Enzymes typically fold into defined 3D protein structures exhibiting a high catalytic efficiency and selectivity. It has been proposed that the earliest enzymes may have arisen from the self-assembly of short peptides into supramolecular amyloid-like structures. Several artificial amyloids have been shown to display catalytic activity while offering advantages over natural enzymes in terms of modularity, flexibility, stability, and reusability. Hydrolases, especially esterases, are the most common artificial amyloid-like nanozymes with some reported to act as carbonic anhydrases (CA). Their hydrolytic activity is often dependent on the binding of metallic cofactors through a coordination triad composed of His residues in the β-strands, which mimic the arrangement found in natural metalloenzymes. Tyr residues contribute to the coordination of metal ions in the active center of metalloproteins; however, their use has been mostly neglected in the design of metal-containing amyloid-based nanozymes. We recently reported that four different polar prion-inspired heptapeptides spontaneously self-assembled into amyloid fibrils. Their sequences lack His but contain three alternate Tyr residues exposed to solvent. We combine experiments and simulations to demonstrate that the amyloid fibrils formed by these peptides can efficiently coordinate and retain different divalent metal cations, functioning as both metal scavengers and nanozymes. The metallized fibrils exhibit esterase and CA activities without the need for a histidine triad. These findings highlight the functional versatility of prion-inspired peptide assemblies and provide a new sequential context for the creation of artificial metalloenzymes. Furthermore, our data support amyloid-like structures acting as ancestral catalysts at the origin of life.
format Online
Article
Text
id pubmed-10510724
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-105107242023-09-21 Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes Navarro, Susanna Díaz-Caballero, Marta Peccati, Francesca Roldán-Martín, Lorena Sodupe, Mariona Ventura, Salvador ACS Nano [Image: see text] Enzymes typically fold into defined 3D protein structures exhibiting a high catalytic efficiency and selectivity. It has been proposed that the earliest enzymes may have arisen from the self-assembly of short peptides into supramolecular amyloid-like structures. Several artificial amyloids have been shown to display catalytic activity while offering advantages over natural enzymes in terms of modularity, flexibility, stability, and reusability. Hydrolases, especially esterases, are the most common artificial amyloid-like nanozymes with some reported to act as carbonic anhydrases (CA). Their hydrolytic activity is often dependent on the binding of metallic cofactors through a coordination triad composed of His residues in the β-strands, which mimic the arrangement found in natural metalloenzymes. Tyr residues contribute to the coordination of metal ions in the active center of metalloproteins; however, their use has been mostly neglected in the design of metal-containing amyloid-based nanozymes. We recently reported that four different polar prion-inspired heptapeptides spontaneously self-assembled into amyloid fibrils. Their sequences lack His but contain three alternate Tyr residues exposed to solvent. We combine experiments and simulations to demonstrate that the amyloid fibrils formed by these peptides can efficiently coordinate and retain different divalent metal cations, functioning as both metal scavengers and nanozymes. The metallized fibrils exhibit esterase and CA activities without the need for a histidine triad. These findings highlight the functional versatility of prion-inspired peptide assemblies and provide a new sequential context for the creation of artificial metalloenzymes. Furthermore, our data support amyloid-like structures acting as ancestral catalysts at the origin of life. American Chemical Society 2023-08-30 /pmc/articles/PMC10510724/ /pubmed/37647583 http://dx.doi.org/10.1021/acsnano.3c04164 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Navarro, Susanna
Díaz-Caballero, Marta
Peccati, Francesca
Roldán-Martín, Lorena
Sodupe, Mariona
Ventura, Salvador
Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
title Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
title_full Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
title_fullStr Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
title_full_unstemmed Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
title_short Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
title_sort amyloid fibrils formed by short prion-inspired peptides are metalloenzymes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510724/
https://www.ncbi.nlm.nih.gov/pubmed/37647583
http://dx.doi.org/10.1021/acsnano.3c04164
work_keys_str_mv AT navarrosusanna amyloidfibrilsformedbyshortprioninspiredpeptidesaremetalloenzymes
AT diazcaballeromarta amyloidfibrilsformedbyshortprioninspiredpeptidesaremetalloenzymes
AT peccatifrancesca amyloidfibrilsformedbyshortprioninspiredpeptidesaremetalloenzymes
AT roldanmartinlorena amyloidfibrilsformedbyshortprioninspiredpeptidesaremetalloenzymes
AT sodupemariona amyloidfibrilsformedbyshortprioninspiredpeptidesaremetalloenzymes
AT venturasalvador amyloidfibrilsformedbyshortprioninspiredpeptidesaremetalloenzymes