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Updated: May 12, 2026

Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability
Published on: June 2, 2023
A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at
Carolin Anders1, Yusuke Higuchi, Kristin Koschinsky
1Chemical Genomics Centre of the Max-Planck-Society, 44227 Dortmund, Germany.
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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