Identifying regulators for EAG1 channels with a novel electrophysiology and tryptophan fluorescence based screen.
BACKGROUND
Ether-à-go-go (EAG) channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG1 channels have no known regulatory ligands.


RESULTS
Here we screened a library of small biologically relevant molecules against EAG1 channels with a novel two-pronged screen to identify channel regulators. In one arm of the screen we used electrophysiology to assess the functional effects of the library compounds on full-length EAG1 channels. In an orthogonal arm, we used tryptophan fluorescence to screen for binding of the library compounds to the isolated C-terminal region.


CONCLUSIONS
Several compounds from the flavonoid, indole and benzofuran chemical families emerged as binding partners and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug discovery for ligand-binding domains of other ion channels.
Brelidze
Tinatin I
TI
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington, United States of America.
Carlson
Anne E
AE
Davies
Douglas R
DR
Stewart
Lance J
LJ
Zagotta
William N
WN
D000818:Animals; D004353:Drug Evaluation, Preclinical; D004594:Electrophysiology / Q000379:methods*; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*
D051638:Ether-A-Go-Go Potassium Channels; D008024:Ligands; D014364:Tryptophan
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