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A partial structure for the γ‐aminobutyric acid (GABA A ) receptor is derived from the model for the nicotinic acetylcholine receptor The anion‐exchange protein of cell membranes is related to the GABA A receptor
Author(s) -
Kosower Edward M.
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)80691-4
Subject(s) - ligand gated ion channel , chemistry , gabaa receptor , chloride channel , cys loop receptors , receptor , acetylcholine receptor , ion channel , biophysics , dids , nicotinic agonist , nicotinic acetylcholine receptor , ligand (biochemistry) , biochemistry , membrane , biology
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 GABA A 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 (GABA A ) 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 GABA A receptor α‐ and β‐subunits reveal at least 4 reasonably homologous sequences. The relationship between AEP and GABA A 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.