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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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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 |
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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 |
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