A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface

C. Anders, Y. Higuchi, K. Koschinsky, M. Bartel, B. Schumacher, P. Thiel, H. Nitta, R. Preisig-Müller, G. Schlichthörl, V. Renigunta, J. Ohkanda, J. Daut, N. Kato, C. Ottmann

Research output: Contribution to journalArticleAcademicpeer-review

55 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)583-593
JournalChemistry & Biology
Volume20
Issue number4
DOIs
Publication statusPublished - 2013

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