Protein refolding based on high hydrostatic pressure and alkaline pH: Application on a recombinant dengue virus NS1 protein.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2019
Historique:
received: 06 09 2018
accepted: 08 01 2019
entrez: 26 1 2019
pubmed: 27 1 2019
medline: 23 10 2019
Statut: epublish

Résumé

In this study we evaluated the association of high hydrostatic pressure (HHP) and alkaline pH as a minimally denaturing condition for the solubilization of inclusion bodies (IBs) generated by recombinant proteins expressed by Escherichia coli strains. The method was successfully applied to a recombinant form of the dengue virus (DENV) non-structural protein 1 (NS1). The minimal pH for IBs solubilization at 1 bar was 12 while a pH of 10 was sufficient for solubilization at HHP: 2.4 kbar for 90 min and 0.4 kbar for 14 h 30 min. An optimal refolding condition was achieved by compression of IBs at HHP and pH 10.5 in the presence of arginine, oxidized and reduced glutathiones, providing much higher yields (up to 8-fold) than association of HHP and GdnHCl via an established protocol. The refolded NS1, 109 ± 9.5 mg/L bacterial culture was recovered mainly as monomer and dimer, corresponding up to 90% of the total protein and remaining immunologically active. The proposed conditions represent an alternative for the refolding of immunologically active recombinant proteins expressed as IBs.

Identifiants

pubmed: 30682103
doi: 10.1371/journal.pone.0211162
pii: PONE-D-18-26214
pmc: PMC6347194
doi:

Substances chimiques

Recombinant Proteins 0
Viral Nonstructural Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0211162

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Rosa Maria Chura-Chambi (RM)

Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, IPEN-CNEN/SP, São Paulo, São Paulo, Brazil.

Cleide Mara Rosa da Silva (CMR)

Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, IPEN-CNEN/SP, São Paulo, São Paulo, Brazil.

Lennon Ramos Pereira (LR)

Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

Paolo Bartolini (P)

Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, IPEN-CNEN/SP, São Paulo, São Paulo, Brazil.

Luis Carlos de Souza Ferreira (LCS)

Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

Ligia Morganti (L)

Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, IPEN-CNEN/SP, São Paulo, São Paulo, Brazil.

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Classifications MeSH