Inhibition of the ethanol-induced potentiation of α1 glycine receptor by a small peptide that interferes with Gβγ binding

Loreto San Martin, Fabian Cerda, Veronica Jimenez, Jorge Fuentealba, Braulio Muñoz, Luis G. Aguayo, Leonardo Guzman

Resultado de la investigación: Contribución a una revistaArtículo

12 Citas (Scopus)

Resumen

Previous studies indicate that ethanol can modulate glycine receptors (GlyR), in part, through Gβγ interaction with basic residues in the intracellular loop. In this study, we show that a seven-amino acid peptide (RQHC7), which has the primary structure of a motif in the large intracellular loop of GlyR (GlyRIL), was able to inhibit the ethanol-elicited potentiation of this channel from 47 ± 2 to 16 ± 4%, without interfering with the effect of Gβγ on GIRK (G protein activated inwardly rectifying potassium channel) activation. RQHC7 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 Gβγ or inhibit ethanol potentiation of GlyR. In silico analysis using docking and molecular dynamics allowed to identify a region of ∼350Å2 involving aspartic acids 186, 228, and 246 in Gβγ where we propose that RQHC7 binds and exerts its blocking action on the effect of ethanol in GlyR.

Idioma originalInglés
Páginas (desde-hasta)40713-40721
Número de páginas9
PublicaciónJournal of Biological Chemistry
Volumen287
N.º48
DOI
EstadoPublicada - 23 nov 2012

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Biología celular
  • Biología molecular

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