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HERO ID
4188612
Reference Type
Journal Article
Title
Cross-linking of sites involved with alcohol action between transmembrane segments 1 and 3 of the glycine receptor following activation
Author(s)
Lobo, IA; Harris, RA; Trudell, JR
Year
2008
Is Peer Reviewed?
Yes
Journal
Journal of Neurochemistry
ISSN:
0022-3042
EISSN:
1471-4159
Volume
104
Issue
6
Page Numbers
1649-1662
Language
English
PMID
18036150
DOI
10.1111/j.1471-4159.2007.05090.x
Web of Science Id
WOS:000253628700019
Abstract
The glycine receptor is a member of the Cys-loop, ligand-gated ion channel family and is responsible for inhibition in the CNS. We examined the orientation of amino acids I229 in transmembrane 1 (TM1) and A288 in TM3, which are both critical for alcohol and volatile anesthetic action. We mutated these two amino acids to cysteines either singly or in double mutants and expressed the receptors in Xenopus laevis oocytes. We tested whether disulfide bonds could form between A288C in TM3 paired with M227C, Y228C, I229C, or S231C in TM1. Application of cross-linking (mercuric chloride) or oxidizing (iodine) agents had no significant effect on the glycine response of wild-type receptors or the single mutants. In contrast, the glycine response of the I229C/A288C double mutant was diminished after application of either mercuric chloride or iodine only in the presence of glycine, indicating that channel gating causes I229C and A288C to fluctuate to be within 6 A apart and form a disulfide bond. Molecular modeling was used to thread the glycine receptor sequence onto a nicotinic acetylcholine receptor template, further demonstrating that I229 and A288 are near-neighbors that can cross-link and providing evidence that these residues contribute to a single binding cavity.
Tags
•
Inorganic Mercury Salts (2)
Mercuric Chloride
Litsearch 1999-2018
Pubmed
WOS
Mercurous Chloride
Litsearch 1999-2018
Pubmed
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