User:Rana Saad/The human GABAb receptor

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Introduction

γ-Aminobutyric acid (GABA)

GABA is the major inhibitory neurotransmitter in the central nervous system (CNS). It plays a key role in modulating neuronal activity since it binds to specific transmembrane receptors (GABAa,GABAb and GABAc) in the plasma membrane of both pre- and postsynaptic neuronal level.

GABAb receptors

Mammalian GABAb receptor is a class C G-protein coupled receptor. Its structure is similar to mGluR ligand binding domain. GABAb is central to inhibitory neurotransmission in the brain and so is considered a good candidate for treatments against alcoholism, stress and number of brain diseases. The GABAb receptor causes the opening of the K+ channels in the postsynaptic membrane, bringing the neuron closer to the equilibrium potential of K+, producing hyperpolarization. As a result the Ca+2 channels in the presynaptic terminal close and neurotransmitter release stops. GABAb can also reduce the activity of adenylyl cyclase and decrease the cell’s conductance to Ca+2

Function

GABAb functions as an obligatory heterodimer subunit of GBR1, which is responsible for ligand-binding. GBR2, on the other hand, is responsible for G protein coupling subunits.

GBR1 and GBR2 subunits structure

Each subunit is a domain of seven-transmembrane helixes, composed of a large extracellular domain - venus flytrap (VFT). VFT contains two lobe-shaped domains: LB1 and LB2, which are connected by three short loops. LB1 and LB2 are αβ-folds composed of central β sheet flanked by an α helix

VFT interaction

Disease

Relevance

Structural highlights

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