Improved HaloTag Ligand Enables BRET Imaging With NanoLuc.

BRET imaging HaloTag Janelia Fluor dyes NanoLuc PKA

Journal

Frontiers in chemistry
ISSN: 2296-2646
Titre abrégé: Front Chem
Pays: Switzerland
ID NLM: 101627988

Informations de publication

Date de publication:
2019
Historique:
received: 14 10 2019
accepted: 23 12 2019
entrez: 30 1 2020
pubmed: 30 1 2020
medline: 30 1 2020
Statut: epublish

Résumé

Bioluminescence resonance energy transfer (BRET) from an exceptionally bright luciferase, NanoLuc, to a fluorescent HaloTag ligand is gaining momentum to monitor molecular interactions. The recommended use of HaloTag618 ligand for the NanoLuc-HaloTag BRET pair is versatile for ensemble experiments due to their well-separated emission bands. However, this system is not applicable for single-cell BRET imaging because of its low BRET efficiency and in turn weak acceptor signals. Here we explored the unprecedented potential of rhodamine based HaloTag ligands, containing azetidine rings, as BRET acceptors. Through a comprehensive evaluation of various commercial and Janelia Fluor HaloTag ligands for improved BRET efficiency and minimal donor signal bleed-through, we identified JF525 to be the best acceptor for microscopic BRET imaging. We successfully employed BRET imaging with JF525 to monitor the interaction of protein kinase A catalytic and regulatory subunit. Single-cell BRET imaging with HaloTag JF525 can henceforth open doors to comprehend and interpret molecular interactions.

Identifiants

pubmed: 31993413
doi: 10.3389/fchem.2019.00938
pmc: PMC6970966
doi:

Types de publication

Journal Article

Langues

eng

Pagination

938

Informations de copyright

Copyright © 2020 Thirukkumaran, Wang, Asouzu, Fron, Rocha, Hofkens, Lavis and Mizuno.

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Auteurs

Ovia Margaret Thirukkumaran (OM)

Laboratory for Biomolecular Network Dynamics, Biochemistry, Molecular and Structural Biology Section, Department of Chemistry, KU Leuven, Heverlee, Belgium.
Chem Tech-Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Congrong Wang (C)

Laboratory for Biomolecular Network Dynamics, Biochemistry, Molecular and Structural Biology Section, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Nnamdi Joseph Asouzu (NJ)

Laboratory for Biomolecular Network Dynamics, Biochemistry, Molecular and Structural Biology Section, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Eduard Fron (E)

Chem Tech-Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Susana Rocha (S)

Chem Tech-Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Johan Hofkens (J)

Chem Tech-Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Luke D Lavis (LD)

Howard Hughes Medical Institute, Ashburn, VA, United States.

Hideaki Mizuno (H)

Laboratory for Biomolecular Network Dynamics, Biochemistry, Molecular and Structural Biology Section, Department of Chemistry, KU Leuven, Heverlee, Belgium.

Classifications MeSH