Cited by 10614-3-3 protein interactionsIon channel regulation and functionCardiac electrophysiology and arrhythmias

A Semisynthetic Fusicoccane Stabilizes a Protein-Protein Interaction and Enhances the Expression of K+ Channels at the Cell Surface

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Anders, Carolin, Higuchi, Yusuke, Koschinsky, Kristin, Bartel, Maria, Schumacher, Benjamin, Thiel, Philipp, Nitta, Hajime, Preisig-Müller, Regina +6 more·2013·Chemistry & Biology

Abstract

Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction. We also tested the functional effects of FC-THF on TASK channels heterologously expressed in Xenopus oocytes. Incubation with 10 μM FC-THF was found to promote the transport of TASK channels to the cell membrane, leading to a significantly higher density of channels at the surface membrane and increased potassium current.

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Crossref · 10.1016/j.chembiol.2013.03.015

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  • Fusicoccanes induce targeted stabilization between 14-3-3 proteins and part of their interactome.

    “Often called ''chemical stabilizers'', fusicoccanes (e.g., fusicoccin A, cotylenin A) induce the targeted stabilization between the 14-3-3 proteins and part of its interactome (Fig. 4).[83][84][85]”

    From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [85]

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Authors
Anders, C., Higuchi, Y., Koschinsky, K., Bartel, M., Schumacher, B., Thiel, P., Nitta, H., Preisig-Müller, R., Schlichthörl, G., Renigunta, V., Ohkanda, J., Daut, J., Kato, N., & Ottmann, C.
Affiliations
  • Max Planck Society (DE)
  • The Institute of Scientific and Industrial Research, The University of Osaka (JP)
  • Philipps University of Marburg (DE)
Corresponding author
  • Daut, Jürgen
  • Kato, Nobuo
  • Ottmann, Christian
Venue
Chemistry & Biology
Publisher
Elsevier BV
Published
2013-04
Volume
20
Issue
4
Pages
583-593
ISSN
1074-5521 (ISSN-L)
OpenAlex
W2159219455
Cited by
106
References
47
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 3 · 2015: 11 · 2014: 9 · 2013: 1
FWCI
3.59
Type
journal article
Language
en
Open access
Locations
  • Chemistry & Biology (publishedVersion)
  • PubMed (publishedVersion)
  • TU/e Research Portal (publishedVersion, other-oa)
  • TU/e Research Portal (submittedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • TU/e Research Portal (submittedVersion, other-oa)
Funders
  • AstraZeneca
  • Merck KGaA
  • Bayer HealthCare
  • Deutsche Forschungsgemeinschaft (SFB593, FOR 1086)
  • National Institute of Biomedical Innovation
  • Bayer CropScience
  • Japan Society for the Promotion of Science (22350074, 24102519)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
14-3-3 proteins, mycotoxins, potassium currents, small molecule binding
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, Biological Transport, Cell Membrane, Diterpenes, Humans, Kinetics, Molecular Conformation, Molecular Sequence Data, Oocytes, Protein Binding, Xenopus laevis, Protein Structure, Tertiary, Crystallography, X-Ray, Potassium Channels, Tandem Pore Domain, 14-3-3 Proteins, Protein Interaction Domains and Motifs, Protein Stability

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