Chromophore pre-maturation for improved speed and sensitivity of split-GFP monitoring of protein secretion.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
22 01 2019
Historique:
received: 01 03 2018
accepted: 22 11 2018
entrez: 24 1 2019
pubmed: 24 1 2019
medline: 23 6 2020
Statut: epublish

Résumé

Complementation-dependent fluorescence is a powerful way to study co-localization or interactions between biomolecules. A split-GFP variant, involving the self-associating GFP 1-10 and GFP 11, has previously provided a convenient approach to measure recombinant protein titers in cell supernatants. A limitation of this approach is the slow chromophore formation after complementation. Here, we alleviate this lag in signal generation by allowing the GFP 1-10 chromophore to mature on a solid support containing GFP 11 before applying GFP 1-10 in analyses. The pre-maturated GFP 1-10 provided up to 150-fold faster signal generation compared to the non-maturated version. Moreover, pre-maturated GFP 1-10 significantly improved the ability of discriminating between Chinese hamster ovary (CHO) cell lines secreting GFP 11-tagged erythropoietin protein at varying rates. Its improved kinetics make the pre-maturated GFP 1-10 a suitable reporter molecule for cell biology research in general, especially for ranking individual cell lines based on secretion rates of recombinant proteins.

Identifiants

pubmed: 30670736
doi: 10.1038/s41598-018-36559-x
pii: 10.1038/s41598-018-36559-x
pmc: PMC6342966
doi:

Substances chimiques

GFP10 Protein 0
Luminescent Proteins 0
Proteins 0
Recombinant Proteins 0
Erythropoietin 11096-26-7
Green Fluorescent Proteins 147336-22-9

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

310

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Auteurs

Magnus Lundqvist (M)

KTH - Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Department of Protein Science, Stockholm, Sweden.

Niklas Thalén (N)

KTH - Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Department of Protein Science, Stockholm, Sweden.

Anna-Luisa Volk (AL)

KTH - Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Department of Protein Science, Stockholm, Sweden.

Henning Gram Hansen (HG)

The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.

Eric von Otter (E)

School of Biological Sciences, Nanyang Technological University, 637551, Singapore, Singapore.

Per-Åke Nygren (PÅ)

KTH - Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Department of Protein Science, Stockholm, Sweden.

Mathias Uhlen (M)

KTH - Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Department of Protein Science, Stockholm, Sweden.
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
KTH - Royal Institute of Technology, Science for Life Laboratory, Stockholm, Sweden.

Johan Rockberg (J)

KTH - Royal Institute of Technology, School of Chemistry, Biotechnology and Health, Department of Protein Science, Stockholm, Sweden. johan.rockberg@biotech.kth.se.

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Classifications MeSH