Amyloid Fibrils Formed by Short Prion-Inspired Peptides Are Metalloenzymes
Navarro, Susanna (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Díaz-Caballero, Marta (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Peccati, Francesca (Centre de Recerca Cooperativa en Biociències)
Roldán-Martín, Lorena (Universitat Autònoma de Barcelona. Departament de Química)
Sodupe Roure, Mariona (Universitat Autònoma de Barcelona. Departament de Química)
Ventura, Salvador (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2023
Abstract:	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.
Grants:	Agencia Estatal de Investigación BIO2017-91475-EXP Agencia Estatal de Investigación PID2020-112715GB-I00 Agencia Estatal de Investigación PID2019-105017RB-I00 Ministerio de Educación, Cultura y Deporte FPU14/05786
Note:	Altres ajuts: acords transformatius de la UAB
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Peptides ; Amyloid fibrils ; Self-assembly ; Nanoenzymes ; Biocatalytic nanomaterials ; Bioremediation
Published in:	ACS nano, Vol. 17, Issue 17 (September 2023) , p. 16968-16979, ISSN 1936-086X

DOI: 10.1021/acsnano.3c04164
PMID: 37647583

12 p, 12.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles