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- Title
Coupling of agonist binding to channel gating in the GABA<sub>A</sub> receptor.
- Authors
Kash, Thomas L.; Jenkins, Andrew; Kelley, Jill C.; Trudell, James R.; Harrison, Neil L.
- Abstract
Neurotransmitters such as acetylcholine and GABA (γ-amino-butyric acid) mediate rapid synaptic transmission by activating receptors belonging to the gene superfamily of ligand-gated ion channels (LGICs)[SUP1]. These channels are pentameric proteins that function as signal transducers, converting chemical messages into electrical signals[SUP2]. Neurotransmitters activate LGICs by interacting with a ligand-binding site[SUP3-7], triggering a conformational change in the protein that results in the opening of an ion channel[SUP8]. This process, which is known as `gating', occurs rapidly and reversibly, but the molecular rearrangements involved are not well understood[SUP9]. Here we show that optimal gating in the GABA[SUBA] receptor, a member of the LGIC superfamily, is dependent on electrostatic interactions between the negatively charged Asp 57 and Asp 149 residues in extracellular loops 2 and 7, and the positively charged Lys 279 residue in the transmembrane 2-3 linker region of the α[SUB1]-subunit. During gating, Asp 149 and Lys 279 seem to move closer to one another, providing a potential mechanism for the coupling of ligand binding to opening of the ion channel.
- Publication
Nature, 2003, Vol 421, Issue 6920, p272
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature01280