PMID: 24909990

 

    Legend: Sugar

Title : Crystal structure of a human GABAA receptor

Abstract :
  1. Type-A γ-aminobutyric acid receptors ( GABAARs ) are the principal mediators of rapid inhibitory synaptic transmission in the human brain
  2. A decline in GABAAR signalling triggers hyperactive neurological disorders such as insomnia, anxiety and epilepsy
  3. Here we present the first three-dimensional structure of a GABAAR, the human β 3 homopentamer, at 3  Å resolution
  4. 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
  5. The receptor was crystallized bound to a previously unknown agonist, benzamidine, opening a new avenue for the rational design of GABAAR modulators
  6. The channel region forms a closed gate at the base of the pore, representative of a desensitized state
  7. These results offer new insights into the signalling mechanisms of pentameric ligand-gated ion channels and enhance current understanding of GABAergic neurotransmission