Paper Citing NAMD - Abstract
San Martin, Loreto; Cerda, Fabian; Jimenez, Veronica; Fuentealba, Jorge; Munoz, Braulio; Aguayo, Luis G.; Guzman, Leonardo
Inhibition of the Ethanol-induced Potentiation of alpha 1 Glycine Receptor by a Small Peptide That Interferes with G beta gamma Binding
JOURNAL OF BIOLOGICAL CHEMISTRY, 287:40713-40721, NOV 23 2012
Previous studies indicate that ethanol can modulate glycine receptors (GlyR), in part, through G beta gamma interaction with basic residues in the intracellular loop. In this study, we show that a seven-amino acid peptide (RQH(C7)), which has the primary structure of a motif in the large intracellular loop of GlyR (GlyR-IL), was able to inhibit the ethanol-elicited potentiation of this channel from 47 +/- 2 to 16 +/- 4%, without interfering with the effect of G beta gamma on GIRK (G protein activated inwardly rectifying potassium channel) activation. RQH(C7) displayed a concentration-dependent effect on ethanol action in evoked and synaptic currents. A fragment of GlyR-IL without the basic amino acids did not interact with G beta gamma or inhibit ethanol potentiation of GlyR. In silico analysis using docking and molecular dynamics allowed to identify a region of similar to 350 angstrom(2) involving aspartic acids 186, 228, and 246 in G beta gamma where we propose that RQH(C7) binds and exerts its blocking action on the effect of ethanol in GlyR.
