Comparative model of a GABAA receptor based on the crystal structure of human β3 homopentamer.

MARÍA JULIA AMUNDARAIN; FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; MARCELO DANIEL COSTABEL

Salto

Congreso; Latin American Crosstalk in Biophysics and Physiology; 2015

Universidad de la Republica

-aminobutyric acid type A receptors, GABAARs, are the major inhibitory neurotransmitter receptors in the mammalian central nervous system. They are members of the Cys-loop family of pentameric ligand gated ion channels. GABAARs are membrane proteins composed of five subunits forming a central chloride-conducting pore. They interact with a variety of ligands, which include GABA, benzodiazepines, neurosteroids and anaesthetics among others, and are involved in several important physiological processes and pathologies.The 3D structure of membrane proteins is particularly difficult to obtain. Only recently it has been published the crystal structure of β3 homopentameric human GABAAR2. We used this structure as a template for homology modelling of the most abundant heteromeric GABAAR channel, the 122 subtype comprising both the extracellular and transmembrane domains. Homology modelling is based on the premise that along evolution tertiarystructure is more conserved than aminoacids? sequence.The development of this model is aimed at studying the Benzodiazepines binding site with a high level of detail. This region is located in the extracellular domain between the 1 and 2 subunits