GABAA receptors are members of the Cys-loop family of ligand-gated ion channels which mediate
most inhibitory neurotransmission in the central nervous system. These receptors are pentameric assemblies of
individual subunits, including α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3. The majority of receptors are comprised of α,
β and γ or δ subunits. Depending on the subunit composition, the receptors are located in either the synapses or
extrasynaptic regions. The most abundant receptors are α1βγ2 receptors, which are activated and modulated by a
variety of pharmacologically and clinically unrelated agents such as benzodiazepines, barbiturates, anaesthetics
and neurosteroids, all of which bind at distinct binding sites located within the receptor complex. However, compared
to αβγ, the binary αβ receptors lack a benzodiazepine α-γ2 interface. In pentameric αβ receptors, the third
subunit is replaced with either an α1 or a β3 subunit leading to two distinct receptors that differ in subunit
stoichiometry, 2α:3β or 3α:2β. The consequence of this is that 3α:2β receptors contain an α-α interface whereas
2α:3β receptors contain a β-β interface. Apart from the replacement of γ by α1 or β3 in binary receptors, the incorporation
of ε subunit into GABAA receptors might be more complicated. As the ε subunit is not only capable
of substituting the γ subunit, but also replacing the α/β subunits, receptors with altered stoichiometry and different
pharmacological properties are produced. The different subunit arrangement of the receptors potentially constructs
novel binding sites which may become new targets of the current or new drugs.
The primary structure of the γ-subunit of the ATPase from Synechocystis
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