A partial structure for the γ-aminobutyric acid (GABAA) receptor is derived from the model for the nicotinic acetylcholine receptor The anion-exchange protein of cell membranes is related to the GABAA receptor

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Abstract

Based on the nicotinic acetylcholine receptor model [(1987) Eur. J. Biochem. 168, 431-449], a partial model is constructed for the exobilayer portion of the GABAA receptor, an approach justified by the superfamily relationship of the two receptors [(1987) Nature 328, 221-227]. The model predicts succesfully the excess positive charge on interior strands which constitute the ligand-responsive portion of the receptor. Binding to GABA expands the exobilayer portion of the receptor, opening a pathway to a chloride channel. Separate binding sites for antianxiolytics (benzodiazepines) and hypnotics (barbiturates) are suggested, with prolongation of chloride entry projected as a consequence of stabilization of the open form. The anion-exchange protein (AEP) of membranes (band 3 of red blood cell membranes) is similar in some respects to the γ-aminobutyric acid (GABAA) receptor. Both proteins are inhibited and labeled by diisocyanatostilbenedisulfonate (DIDS), both transport Cl- and HCO-3, and both are membrane proteins. Starting with the lysines known to be labeled in band 3 protein, searches of the amino acid sequences of the GABAA receptor α- and β-subunits reveal at least 4 reasonably homologous sequences. The relationship between AEP and GABAA receptor leads to the idea that the chloride/bicarbonate channel may be the ancestor of all ligand-gated channels, with ligand gating by γ-aminobutyric acid and acetylcholine arising later in evolution.

Original languageEnglish
Pages (from-to)5-10
Number of pages6
JournalFEBS Letters
Volume231
Issue number1
DOIs
StatePublished - 11 Apr 1988

Keywords

  • Amino acid sequence
  • Anion-exchange protein
  • GABA receptor
  • Nicotinic acetylcholine receptor
  • Sequence homology
  • Structural model

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