GABA receptor: Difference between revisions

Ionotropic and metabotropic are the two major classes of GABA receptors abundant throughout neuronal cells (Cryan, 2005). Metabotropic GABAB receptors induce a change in membrane potential through the action of a second messenger pathway (Kerr, 1995). The GABAB receptor functions as a heterodimer of two subunits, GABAB1 (grey)  and GABAB2 (green). Heterodimerization is accomplished through interactions of the coiled-coil motifs within the C-termini and interactions between the transmembrane and extracellular domains (Cryan, 2005). Additionally, there are two GABAB1 isoforms that differ at the N-termini where there are two sushi domains (Cryan, 2005). These sushi domains on the GABAB1 subunit are key to the receptor's interaction with other proteins as well as axonal signaling (Cryan, 2005). The two GABAB subunits link together in the endoplasmic reticulum as GABAB2 connects to GABAB1 via their intracellular C-termini to form the heterodimer GABAB receptor (Gumerov, 2015).  

The GABAB receptor exists in the <scene name='71/716457/Gabab_rest/1'>resting state</scene> (PDB: 4MQE) and the <scene name='71/716457/Active_state/1'>active state</scene> (PDB: 4MS3)(Geng, 2013). Using the GABAB crystal structures, Geng et al. found that both subunits exist in open conformations while at rest. Upon binding with the agonist the GABAB1 subunit closes (Geng, 2013). Additionally, it was found that the agonist (i.e. GABA) is bound to the <scene name='71/716457/Active_site_iwith_gaba_bound/1'>active site</scene>, located at the interdomain crevice of the GABAB1 subunit due to an overlap of amino acid residues (Geng, 2013). This conformation change is noted by the visible reduction in space between GABAB subunits upon binding with GABA.