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Identification of an amino acid sequence within GABA A receptor β 3 subunits that is important for receptor assembly
Author(s) -
Ehya Noosha,
Sarto Isabella,
Wabnegger Leila,
Klausberger Thomas,
Sieghart Werner
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01509.x
Subject(s) - cys loop receptors , protein subunit , g alpha subunit , receptor , interleukin 10 receptor, alpha subunit , gamma aminobutyric acid receptor subunit alpha 1 , peptide sequence , biology , biochemistry , sequence (biology) , gabaa receptor , amino acid , chemistry , acetylcholine receptor , nicotinic acetylcholine receptor , gene
GABA A receptors are chloride ion channels that can be opened by GABA, the most important inhibitory transmitter in the CNS. In the mammalian brain the majority of these pentameric receptors is composed of two α, two β and one γ subunit. To achieve the correct order of subunits around the pore, each subunit must form specific contacts via its plus (+) and minus (–) side. To identify a sequence on the β 3 subunit important for assembly, we generated various full‐length or truncated chimeric β 3 constructs and investigated their ability to assemble with α 1 and γ 2 subunits. It was demonstrated that replacement of the sequence β 3 (76–89) by the homologous α 1 sequence impaired assembly with α 1 but not with γ 2 subunits in α 1 β 3 γ 2 ‐GABA A receptors. Other experiments indicated that assembly was impaired via the β 3 (–) side of the chimeric subunit. Within the sequence β 3 (76–89) the sequence β 3 (85–89) seemed to be of primary importance for assembly with α 1 subunits. A comparison with the structure of the acetylcholine‐binding protein supports the conclusion that the sequence β 3 (85–89) is located at the β 3 (–) side and indicates that it contains amino acid residues that might directly interact with the (+) side of the neighbouring α 1 subunit.