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Titolo:
NICOTINIC RECEPTOR - AN ALLOSTERIC PROTEIN SPECIALIZED FOR INTERCELLULAR COMMUNICATION
Autore:
BERTRAND D; CHANGEUX JP;
Indirizzi:
CTR MED UNIV GENEVA,DEPT PHYSIOL,1 RUE MICHEL SERVET CH-1211 GENEVA 4SWITZERLAND INST PASTEUR,CNRS,UA D1284 F-75724 PARIS 15 FRANCE
Titolo Testata:
Seminars in the neurosciences
fascicolo: 2, volume: 7, anno: 1995,
pagine: 75 - 90
SICI:
1044-5765(1995)7:2<75:NR-AAP>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
AGONIST-BINDING-SITE; RAT CENTRAL NEURONS; OUTER HAIR-CELLS; ACETYLCHOLINE-RECEPTOR; ALPHA-SUBUNIT; CHANNEL DOMAIN; ION CHANNEL; DELTA-SUBUNIT; AMINO-ACIDS; NONCOMPETITIVE ANTAGONIST;
Keywords:
NICOTINIC ACETYLCHOLINE RECEPTOR ION CHANNEL; SYNAPSE; ALLOSTERIC MODEL;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
124
Recensione:
Indirizzi per estratti:
Citazione:
D. Bertrand e J.P. Changeux, "NICOTINIC RECEPTOR - AN ALLOSTERIC PROTEIN SPECIALIZED FOR INTERCELLULAR COMMUNICATION", Seminars in the neurosciences, 7(2), 1995, pp. 75-90

Abstract

The nicotinic acetylcholine receptor is the prototype of a superfamily of ligand-gated channels and shares with the other members of the family, such as glycine, GABA and the 5HT(3) receptor, many structural features including its transmembrane organization. They are integral membrane proteins made up of the assembly of five subunits each of them spanning four times the membrane. Up to now, 9 alpha, 3 beta, 1 gamma,1 delta and 1 epsilon subunits have been identified and cloned. Sequence homologies suggest that they derive from a common ancestor. Strongevidence, however supports the view that other subunits whose function is unknown are still missing. Affinity labeling and site-directed mutagenesis of the agonist binding site reveal that the agonist binds atthe interface between two adjacent alpha-and non-alpha subunits. Structural and and functional studies point to the major contribution of the transmembrane segment M2 to the formation of the ionic pore, the properties of which depend critically on amino acid residues which face the channel lumen and are aligned along the meridian of an alpha-helix. Assembly of differents subunits into a pseudo-symmetrical heteropentamer results in a large number of combinations of receptors which may differ by their physiological and/or pharmacological properties. Several regulatory properties of the nicotinic acetylcholine receptors (as well as those of other ligand-gated channels) can be accounted for by an adapted version of the allosteric model. According to this model, binding of the agonist stabilizes one (or more) conformational state(s), and thus indirectly causes channel opening and/or desensitization. Short-term modulation of the efficacy of these receptors can also be explained on the basis of this model assuming that modulatory ligands act as allosteric effectors which preferentially stabilize defined conformational states when they bind at allosteric sites topologically distinct from the agonist binding site.

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Documento generato il 05/07/20 alle ore 06:09:04