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Titolo:
Identification of a new ligand binding domain in the al subunit of the inhibitory glycine receptor
Autore:
Vafa, B; Lewis, TM; Cunningham, AM; Jacques, P; Lynch, JW; Schofield, PR;
Indirizzi:
Garvan Inst Med Res, Sydney, NSW 2010, Australia Garvan Inst Med Res Sydney NSW Australia 2010 Sydney, NSW 2010, Australia
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 5, volume: 73, anno: 1999,
pagine: 2158 - 2166
SICI:
0022-3042(199911)73:5<2158:IOANLB>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
NICOTINIC ACETYLCHOLINE-RECEPTOR; SITE-DIRECTED MUTAGENESIS; ION-CHANNEL RECEPTORS; ALPHA-SUBUNIT; AGONIST-BINDING; AMINO-ACIDS; FUNCTIONAL EXPRESSION; GABA(A) RECEPTOR; MOTOR IMPAIRMENT; XENOPUS OOCYTES;
Keywords:
glycine receptor; ligand-gated ion channel receptor neurotransmitter; mutagenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Schofield, PR Garvan Inst Med Res, 384 Victoria St, Sydney, NSW 2010, Australia Garvan Inst Med Res 384 Victoria St Sydney NSW Australia 2010
Citazione:
B. Vafa et al., "Identification of a new ligand binding domain in the al subunit of the inhibitory glycine receptor", J NEUROCHEM, 73(5), 1999, pp. 2158-2166

Abstract

Four discontinuous extracellular sequence domains have been proposed to form the ligand binding sites of the ligand-gated ion channel receptor superfamily. In this study, we investigated the role of 12 contiguous residues ofthe inhibitory glycine receptor that define the proposed "loop A" ligand binding domain; Using the techniques of site-directed mutagenesis and patch-clamp electrophysiology, four of the 12 residues were shown to have impaired ligand binding. Three mutants, I93A, A101H, and N102A, resulted in significant (17-44-fold) increases in the agonist EC50 values as compared with the wild-type glycine receptor, whereas Hill coefficients, I-max values, and antagonist affinity remained largely unaffected. Consideration of receptor efficacy values indicates that these residues are involved in ligand binding rather than channel activation. A fourth mutant, W94A, failed to give rise to any glycine-activated currents, although cell-surface expression was observed, suggesting that this residue may also be involved in agonist binding. These data provide the most extensive characterization of the loop A ligand binding domain available to date and define two new residue locations,Ile(93) and Asn(102), as contributing to the four-loop model of ligand binding.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 09:06:10