Crystal Structure Of The Gabaa Ionotropic Receptor

This short article briefly describes the structure of the ionotropic GABAA receptor. The GABAA receptor is a Cl- permeable ion channel extensively expressed in the postsynaptic membrane of inhibitory central nervous system neurons. The binding of GABA opens the receptor-associated ion channel, leading to the influx of Cl- ions into the intracellular space. This leads to the hyperpolarisation of the neuronal membrane, inhibits neuronal transmission, and decreases the probability of action potential firing.
Note that GABAA transmission may be excitatory in some neurons during some stages of neuronal developement. Whether the opening of GABAA receptors will lead to efflux or infux of Cl- ions depends on the equilibrium potential for Cl-, which is set by manipulating the Cl- concentration gradient across the neuronal membrane.
The GABAA channel is a member of the cys-loop receptor family. The ion-permeating pore of the channel is surrounded by five protein subunits, which carefully assemble within the synaptic membrane. The assembly of these subunits leads to the formation of the channel pore, ion selectivity filter, ligand binding sites, neurotransmitter binding sites and regulatory motifs, and other functional domains.
The figure below shows the ribbon structure of two adjacent GABAA receptor subunits (blue and red). The upper regions of the protein are formed of beta-pleated sheet secondary structures arranged in a beta-sandwich. These are the regions of the channel exposed to the extracellular solution. The alpha-helical regions of the channel are anchored within the synaptic membrane. The neurotransmitter binding site (green) is located at the interface of the two subunits, and faces the extracellular solution.


The neurotransmitter binding event induces a change in the 3D structure of the protein, which eventually leads to the opening of the channel pore, and permeation of the Cl- ions in or out of the cell. The tight coupling between the extracellular domain and transmembrane domains of the GABAA receptor allows for the neurontramitter binding event to be transduced to the channel pore. In the figure below the neurotransmitter is shown as a cyan sphere. The full molecular structure is shown for the amino acids important in the transduction of the ligand-binding event to the channel pore.