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: Article

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

Huella dactilar

Glycine Receptors
Ethanol
Peptides
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Inwardly Rectifying Potassium Channel
Basic Amino Acids
Molecular Dynamics Simulation
GTP-Binding Proteins
Aspartic Acid
Computer Simulation
Molecular dynamics
Chemical activation
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Citar esto

San Martin, Loreto ; Cerda, Fabian ; Jimenez, Veronica ; Fuentealba, Jorge ; Muñoz, Braulio ; Aguayo, Luis G. ; Guzman, Leonardo. / Inhibition of the ethanol-induced potentiation of α1 glycine receptor by a small peptide that interferes with Gβγ binding. En: Journal of Biological Chemistry. 2012 ; Vol. 287, N.º 48. pp. 40713-40721.
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Inhibition of the ethanol-induced potentiation of α1 glycine receptor by a small peptide that interferes with Gβγ binding. / San Martin, Loreto; Cerda, Fabian; Jimenez, Veronica; Fuentealba, Jorge; Muñoz, Braulio; Aguayo, Luis G.; Guzman, Leonardo.

En: Journal of Biological Chemistry, Vol. 287, N.º 48, 23.11.2012, p. 40713-40721.

Resultado de la investigación: Article

TY - JOUR

T1 - Inhibition of the ethanol-induced potentiation of α1 glycine receptor by a small peptide that interferes with Gβγ binding

AU - San Martin, Loreto

AU - Cerda, Fabian

AU - Jimenez, Veronica

AU - Fuentealba, Jorge

AU - Muñoz, Braulio

AU - Aguayo, Luis G.

AU - Guzman, Leonardo

PY - 2012/11/23

Y1 - 2012/11/23

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AB - 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.

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