Charge and geometry of residues in the loop 2 β hairpin differentially affect agonist and ethanol sensitivity in glycine receptors.

ABSTRACT: Recent studies highlighted the importance of loop 2 of α1 glycine receptors (GlyRs) in the propagation of ligand-binding energy to the channel gate. Mutations that changed polarity at position 52 in the β hairpin of loop 2 significantly affected sensitivity to ethanol. The present study extends the investigation to charged residues. We found that substituting alanine with the negative glutamate at position 52 (A52E) significantly left-shifted the glycine concentration response curve and increased sensitivity to ethanol, whereas the negative aspartate substitution (A52D) significantly right-shifted the glycine EC₅₀ but did not affect ethanol sensitivity. It is noteworthy that the uncharged glutamine at position 52 (A52Q) caused only a small right shift of the glycine EC₅₀ while increasing e

SUBMITTER: Perkins DI 

PROVIDER: S-EPMC3336819 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature