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| CHANNEL GATING GOVERNED SYMMETRICALLY BY CONSERVED LEUCINE RESIDUES IN THE M2 DOMAIN OF NICOTINIC RECEPTORS |
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| Author(s): LABARCA C, NOWAK MW, ZHANG HY, TANG LX, DESHPANDE P, LESTER HA |
| Source: NATURE Volume: 376 Issue: 6540 Pages: 514-516 Published: AUG 10 1995 |
| Times Cited: 193 References: 15 |
| Abstract: IN nicotinic acetylcholine receptors (nAChR), as well as glycine, GABA(A) (gamma-aminobutyric acid), serotonin (5-HT3), and GluCl glutamate receptors, a leucine residue at the approximate midpoint of the M2 transmembrane domain (the 9' position(1)) is conserved across most known subunits(2). Structural data for the nAChR suggest that the Leu 9' residues occupy a 'kink' in each of the five M2 helices and point into the closed channel; in the opening step, the M2 helices rotate so that Leu 9' side chains no longer occlude the conduction pathway(3), Mutation of Leu 9' to one of several other residues slows desensitization and increases sensitivity to agonist(4-6). We have exploited the alpha(2) beta gamma delta stoichiometry of muscle nAChR to express receptors with m(s)* = 0 to 5 Leu 9'Scr mutated subunits. Strikingly, each Leu 9'Ser mutation shifts the dose-response relation for ACh to the left by similar to 10-fold; a nAChR with m(s)* = 4 is 10(4)-fold more sensitive than the wild type, The results suggest that each of the five Leu 9' residues participates independently and symmetrically in a key step in the structural transition between the closed and open states. |
| Document Type: Article |
| Language: English |
| Reprint Address: LABARCA, C (reprint author), CALTECH, DIV BIOL, PASADENA, CA 91125 USA |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: RN622 |
| ISSN: 0028-0836 |
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