Surpassing protein specificity in biomimetics of bacterial amyloids
Sanchez, Julieta M. (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Voltà-Durán, Eric (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Parladé Molist, Eloi (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Mangues, Ramon 1957- (Institut de Recerca Sant Pau)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Unzueta Elorza, Ugutz (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2025
Abstract:	In nature, nontoxic protein amyloids serve as dynamic, protein-specific depots, exemplified by both bacterial inclusion bodies and secretory granules from the endocrine system. Inspired by these systems, chemically defined and regulatory-compliant artificial protein microgranules have been developed for clinical applications as endocrine-like protein repositories. This has been achieved by exploiting the reversible coordination between histidine residues and divalent cations such as Zn, that promotes protein-protein interactions. While stereospecificity is a main architectonic feature of natural amyloids, the potential for synthetic approaches to create hybrid protein materials remains unexplored. Such materials could enable the occurrence and synchronized local application of diverse proteins in predefined molar ratios, for coupled enzymatic reactions or delivery of synergistically acting polypeptides. Here, we report on the fabrication of artificial protein granules with amyloidal architecture formed by combining two structurally distinct polypeptides. Specifically, we tested co-aggregation of the pairs GFP/IRFP and GFP/β-galactosidase. The formation of hybrid microparticles was confirmed through FRET and complementary methodologies, demonstrating that the His-Zn clustering technology does not require sequential or structural homologies between aggregating polypeptides. This approach opens new avenues for the development of functional depots that capitalize on synergistic protein functionalities, paving the way for next-generation functional materials.
Grants:	Agencia Estatal de Investigación PDC2022-133858-I00 Agencia Estatal de Investigación PID2022-1368450 Agencia Estatal de Investigación PID2019-105416RB-I00 Ministerio de Sanidad y Consumo CB06/01/0014 Ministerio de Sanidad y Consumo CB06/01/1031 Instituto de Salud Carlos III PI23/00318 Instituto de Salud Carlos III PI20/00400 Instituto de Salud Carlos III CP19/00028 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00092
Note:	Altres ajuts: acords transformatius de la UAB
Note:	Altres ajuts: JMS is supported with a María Zambrano postdoctoral researcher contract (677904) from Ministerio de Universidades and European Union ("Financed by European Union-Next GenerationEU").
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Recombinant protein ; Microparticles ; Amyloids ; Biomimetics ; Protein materials
Published in:	International journal of biological macromolecules, Vol. 296 (March 2025) , art. 139635, ISSN 1879-0003

DOI: 10.1016/j.ijbiomac.2025.139635

Available from: 2026-03-30 Postprint

The record appears in these collections:
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