Year: 2017
Type: article
Abstract: The major isoform of the GABA A receptor is α 1 β 2 γ 2 . The binding sites for the agonist GABA are located at the β 2 +/α 1 − subunit interfaces and the modulatory site for benzodiazepines at α 1 +/γ 2 −. In the absence of α 1 subunits, a receptor was formed that was gated by GABA and modulated by diazepam similarly. This indicates that alternative subunits can take over the role of the α 1 subunits. Point mutations were introduced in β 2 or γ 2 subunits at positions homologous to α 1 − benzodiazepine binding and GABA binding positions, respectively. From this mutation work we conclude that the site for GABA is located at a β 2 +/β 2 − subunit interface and that the diazepam site is located at the β 2 +/γ 2 − subunit interface. Computational docking leads to a structural hypothesis attributing this non-canonical interaction to a binding mode nearly identical with the one at the α 1 +/γ 2 − interface. Thus, the β 2 subunit can take over the role of the α 1 subunit for the formation of both sites, its minus side for the GABA binding site and its plus side for the diazepam binding site.
Source: Scientific Reports
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W2767629627