Aggregation-prone peptides modulate activity of bovine interferon gamma released from naturally occurring protein nanoparticles
Visualitza/Obre
Autor/a
Carratalá, José Vicente
Cano‐Garrido, Olivia
Sánchez, Julieta
Membrado, Cristina
Pérez, Eudald
Conchillo‐Solé, Oscar
Daura, Xavier
Sánchez‐Chard, Alejandro
Villaverde, Antonio
Arís, Anna
Garcia‐Fruitós, Elena
Ferrer‐Miralles, Neus
Data de publicació
2020-02-03ISSN
1871-6784
Resum
Efficient protocols for the production of recombinant proteins are indispensable for the development of the biopharmaceutical sector. Accumulation of recombinant proteins in naturally-occurring protein aggregates is detrimental to biopharmaceutical development. In recent years, the view of protein aggregates has changed with the recognition that they are a valuable source of functional recombinant proteins. In this study, bovine interferon-gamma (rBoIFN-γ) was engineered to enhance the formation of protein aggregates, also known as protein nanoparticles (NPs), by the addition of aggregation-prone peptides (APPs) in the generally recognized as safe (GRAS) bacterial Lactococcus lactis expression system. The L6K2, HALRU and CYOB peptides were selected to assess their intrinsic aggregation capability to nucleate protein aggregation. These APPs enhanced the tendency of the resulting protein to aggregate at the expense of total protein yield. However, fine physico-chemical characterization of the resulting intracellular protein NPs, the protein released from them and the protein purified from the soluble cell fraction indicated that the compactability of protein conformations was directly related to the biological activity of variants of IFN-γ, used here as a model protein with therapeutic potential. APPs enhanced the aggregation tendency of fused rBoIFN-γ while increasing compactability of protein species. Biological activity of rBoIFN-γ was favored in more compacted conformations. Naturally-occurring protein aggregates can be produced in GRAS microorganisms as protein depots of releasable active protein. The addition of APPs to enhance the aggregation tendency has a positive impact in overall compactability and functionality of resulting protein conformers.
Tipus de document
Article
Versió del document
Versió acceptada
Llengua
English
Matèries (CDU)
63 - Agricultura. Silvicultura. Zootècnia. Caça. Pesca
Pàgines
45
Publicat per
Elsevier
Publicat a
New Biotechnology
Citació
Carratalá, José Vicente, Olivia Cano-Garrido, Julieta Sánchez, Cristina Membrado, Eudald Pérez, Oscar Conchillo-Solé, and Xavier Daura et al. 2020. "Aggregation-Prone Peptides Modulate Activity Of Bovine Interferon Gamma Released From Naturally Occurring Protein Nanoparticles". New Biotechnology 57: 11-19. Elsevier BV. doi:10.1016/j.nbt.2020.02.001.
Número de l'acord de la subvenció
INIA/Programa Estatal de I+D+I orientada a los retos de la sociedad/RTA2015-00064-C02-01/ES/Validación del uso de las proteínas M-SAA3 y MMP-9 en la mejora del secado de la vaca de leche y optimización de su dosis efectiva mediante su nanoestructuración/
INIA/Programa Estatal de I+D+I orientada a los retos de la sociedad/RTA2015-00064-C02-02/ES/Validación del uso de las proteínas M-SAA3 y MMP-9 en la mejora del secado de la vaca de leche y optimización de su dosis efectiva mediante su nanoestructuración/
Programa
Producció de Remugants
Aquest element apareix en la col·lecció o col·leccions següent(s)
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