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

MARÍA J. AMUNDARAIN; FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; MARCELO D. COSTABEL

Salto

Workshop; VIII PosLatAm course: Membrane Lipids, Transporters, Channels?and all that crosstalk and Latin American Crosstalk in Biophysics and Physiology; 2015

Sociedad de Biofísica Uruguaya y Sociedad Argentina de Biofísica

n-aminobutyric acid type A receptors, GABAARs, are the major inhibitory neurotransmitter receptors in the mammalian central nervous system. They aremembers of the Cys-loop family of pentameric ligand gated ion channels. GABAARs are membrane proteins composed of five subunits forming acentral chloride-conducting pore. They interact with a variety of ligands, which include GABA, benzodiazepines, neurosteroids and anaesthetics amongothers, and are involved in several important physiological processes and pathologies.1The 3D structure of membrane proteins is particularly difficult to obtain. Only recently it has been published the crystal structure of β3 homopentamerichuman GABAAR2. We used this structure as a template for homology modelling of the most abundant heteromeric GABAAR channel, the 122subtype comprising both the extracellular and transmembrane domains (Fig. 2). 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 extracellulardomain between the 1 and 2 subunits