Referenced in: none

Automatically associated channels: TASK1 , TASK3

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

Authors: Carolin Anders, Yusuke Higuchi, Kristin Koschinsky, Maria Bartel, Benjamin Schumacher, Philipp Thiel, Hajime Nitta, Regina Preisig-Müller, Günter Schlichthörl, Vijay Renigunta, Junko Ohkanda, Jürgen Daut, Nobuo Kato, Christian Ottmann

Journal, date & volume: Chem. Biol., 2013 Apr 18 , 20, 583-93

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23601647

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.