Abstract
Serine 171 in the GABA(A) receptor gamma2 subunit is highly conserved in the ligand-gated ion channel superfamily. In this paper, we report that mutating serine 171 within gamma2 to glycine or cysteine prevents the interaction of gamma2 with alpha2 and beta1 when these subunits are co-expressed in human embryo kidney 293 cells, resulting in intracellular retention of gamma2. Structure analysis based on a three-dimensional homology model of gamma2 (Ernst, M., Brauchart, D., Boresch, S., and Sieghart, W. (2003) Neuroscience 119, 933-943) reveals that serine 171 may play a critical role in the formation and stabilization of an exposed turn structure that is part of the subunit interaction site. Mutation of serine 171 in the gamma2 subunit could therefore result in alteration of the structure of the subunit interaction site, preventing correct subunit assembly.
Highlights
␥-Aminobutyric acid type A (GABAA)1 receptors are members of the ligand-gated ion channel superfamily, which includes nicotinic acetylcholine (ACh), glycine, glutamate, and 5-hydroxytryptamine type 3 (5HT3) receptors
Structure analysis based on a three-dimensional homology model of ␥2 (Ernst, M., Brauchart, D., Boresch, S., and Sieghart, W. (2003) Neuroscience 119, 933–943) reveals that serine 171 may play a critical role in the formation and stabilization of an exposed turn structure that is part of the subunit interaction site
In the present study, using single amino acid substitutions, we further demonstrate that serine 171 within ␥2 plays a critical role in mediating the subunit interaction and cell surface expression of ␥2, whereas tyrosine 172, as well as other residues surrounding Ser-171/ Tyr-172, exhibit little or no effect on the function of the ␥2 subunit
Summary
␥-Aminobutyric acid type A (GABAA)1 receptors are members of the ligand-gated ion channel superfamily, which includes nicotinic acetylcholine (ACh), glycine, glutamate, and 5-hydroxytryptamine type 3 (5HT3) receptors. In the present study, using single amino acid substitutions, we further demonstrate that serine 171 within ␥2 plays a critical role in mediating the subunit interaction and cell surface expression of ␥2, whereas tyrosine 172, as well as other residues surrounding Ser-171/ Tyr-172, exhibit little or no effect on the function of the ␥2 subunit.
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