Aggregation-prone peptides modulate activity of bovine interferon gamma released from naturally occurring protein nanoparticles
This document contains embargoed files until 2021-02-02
Carratalá, José Vicente
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.
63 - Agricultura. Silvicultura. Zootècnia. Caça. Pesca
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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.
Grant agreement number
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/
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