Title : Crystal structure of a human
GABAA receptor
Abstract :
- Type-A γ-aminobutyric acid receptors ( GABAARs ) are the principal mediators of rapid inhibitory synaptic transmission in the human brain
- A decline in GABAAR signalling triggers hyperactive neurological disorders such as insomnia, anxiety and epilepsy
- Here we present the first three-dimensional structure of a GABAAR, the human β 3 homopentamer, at 3 Å resolution
- This structure reveals architectural elements unique to eukaryotic Cys-loop receptors , explains the mechanistic consequences of multiple human disease mutations and shows an unexpected structural role for a conserved N-linked glycan
- The receptor was crystallized bound to a previously unknown agonist, benzamidine, opening a new avenue for the rational design of GABAAR modulators
- The channel region forms a closed gate at the base of the pore, representative of a desensitized state
- These results offer new insights into the signalling mechanisms of pentameric ligand-gated ion channels and enhance current understanding of GABAergic neurotransmission
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):