期刊
CHEMISTRY & BIOLOGY
卷 20, 期 4, 页码 583-593出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2013.03.015
关键词
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资金
- AstraZeneca
- Bayer CropScience
- Bayer Healthcare
- Boehringer Ingelheim
- Merck KGaA
- Deutsche Forschungsgemeinschaft [SFB593, TP4, FOR1086, TP7]
- Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, Japan
- Excellent Young Researcher Overseas Visit Program of the Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [24102519, 22350074] Funding Source: KAKEN
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 mu M 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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