GABAA receptor family: overview on structural characterization

Abstract

The pentameric γ-aminobutyric acid type A receptors are ion channels activated by ligands, which intervene in the rapid inhibitory transmission in the mammalian CNS. Due to their rich pharmacology and therapeutic potential, it is essential to understand their structure and function thoroughly. This deep characterization was hampered by the lack of experimental structural information for many years. Thus, computational techniques have been extensively combined with experimental data, in order to undertake the study of γ-aminobutyric acid type A receptors and their interaction with drugs. Here, we review the exciting journey made to assess the structures of these receptors and outline major outcomes. Finally, we discuss the brand new structure of the α₁β₂γ₂ subtype and the amazing advances it brings to the field.

Keywords: Cys-loop receptors; GABAAR; comparative modeling; cryo-EM; gamma-aminobutyric acid receptor; homology modeling; pentameric ligand-gated ion channels (pLGICs); structure determination; x-ray crystallography.