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

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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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14-3-3 Proteins
Crystallography
Proteins
Mycotoxins
Potassium Channels
Cell membranes
Xenopus
Oocytes
Potassium
Stabilization
Cell Membrane
Derivatives
Membranes
Molecules

Cite this

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. / A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface. In: Chemistry & Biology. 2013 ; Vol. 20, No. 4. pp. 583-593.
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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",
author = "C. Anders and Y. Higuchi and K. Koschinsky and M. Bartel and B. Schumacher and P. Thiel and H. Nitta and R. Preisig-M{\"u}ller and G. Schlichth{\"o}rl and V. Renigunta and J. Ohkanda and J. Daut and N. Kato and C. Ottmann",
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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 2013, 'A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface', Chemistry & Biology, vol. 20, no. 4, pp. 583-593. https://doi.org/10.1016/j.chembiol.2013.03.015

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

In: Chemistry & Biology, Vol. 20, No. 4, 2013, p. 583-593.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface

AU - Anders, C.

AU - Higuchi, Y.

AU - Koschinsky, K.

AU - Bartel, M.

AU - Schumacher, B.

AU - Thiel, P.

AU - Nitta, H.

AU - Preisig-Müller, R.

AU - Schlichthörl, G.

AU - Renigunta, V.

AU - Ohkanda, J.

AU - Daut, J.

AU - Kato, N.

AU - Ottmann, C.

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AB - 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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DO - 10.1016/j.chembiol.2013.03.015

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SP - 583

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JO - Chemistry & Biology

JF - Chemistry & Biology

SN - 1074-5521

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