The homologous sequence and structure allows homology modeling of the various functional domains of GABAA-Rs using the structures of the AChBP and the nAChR as templates (Cromer et al., 2002; Ernst et al., 2003; Ernst et al., 2005). The resulting models not only identified the absolute arrangement of the 1γ, 2α and 2β subunits within the receptor, but also the structural features of the extracellular domain and their binding pockets. In the extracellular domain, there are 5 pockets at the 5 subunit interfaces. The two pockets at the β/α interfaces form the 2 GABA binding sites, and the pocket at the α/γ interface forms the benzodiazepine binding site. The GABA pocket is formed by the so-called “loops” A, B, and C of the β+ (“principal”) side and the so-called “loops” D, E, and F of the α- (“complementary”) side (Ernst et al., 2003). Residues homologous to those in the agonist binding loops at the β/α interface, are homologous in all members of the superfamily (Smith & Olsen, 1995; Sigel & Buhr, 1997; Corringer et al., 2000) and are also homologous
