Amino acid sequence nicotinic acetylcholine receptor

The elucidation of the amino acid sequence of many channels now allows structural and phylogenetic comparisons. The nicotinic acetylcholine receptor (AchR) Na" -channel,... 

Similar nAChRs are also found in the brain.621 631 632 However, they are not identical but have at least 17 differing amino acid sequences (al-alO, (31-(34, y, 8, and e). The neuromuscular junction receptor (muscle type) from fish is described as (al)2 (31 my / S.626 The brain contains homopentamers of subunits a7, a8, and a9 as well as various heteropentamers. The various forms possess different affinities for acetylcholine and for antagonists such as nicotine.633 634 In the brain the highest affinity for nicotine is shown by an a4 32 form, which represents over 80% of the nAChR in mammalian brain.634 635 Knockout mice in which the (32 subunit gene has been deleted lose their sensitivity to nicotine. 

The muscarinic cholinergic system has quite a different mode of operation in that the receptor is connected to the final action by a chain of events. Thus its response is slower than the nicotinic, where the receptor and ion channel are closely connected. Five distinct muscarinic receptors have been identified in mammals, based on anatomical location, genetic analysis, function, and amino acid sequence. All of them have seven transmembrane domains [166, 167, 168, 169]. The N- terminal domain outside the cell binds acetylcholine or other ligands at a site that includes an aspartate residue, while the C-terminal domain inside the cell is coupled to a so-called G-protein , which is initially bound to guanosine diphosphate (GDP), but exchanges it for guanosine triphosphate (GTP) when activated by its transmitter. The activated G-protein then activates phospholipase C, which hydrolyzes phosphoinositides to release 1,4,5-inositol triphosphate [170]. The final action depends on which type of cell is involved so that in some types ion channels are opened just as with the nicotinic receptor, but in other cases other processes are affected, for example the release of dopamine [171]. Since there are these differences... 

Table I. Amino acid sequences in loop D of vertebrate and insect nicotinic acetylcholine receptors.

P), 60,000 (56,279) (y) and 65,000 (57,565) (6) (the first value is from SDS the value in brackets is the exact M, based on amino acid composition) in the ratio 2 1 1 1, with an average 40% amino-acid sequence identity between all 4 chains [B.M.Conti-Troconi et al. Science 218 (1982) 1227-1229]. DNA for all 4 subunits has been cloned and sequenced [M. Noda et al. Nature 301 (1983) 251-254]. The covalent affinity probes, [ H]-bromoacetylcholine and 4-(AI-maleiniideo)- H tenzyl trimethylammonium iodide, label the a-subunit by reacting with cysteine residues 192 and 193. Thus, each of ffie two a-subunits carries an acetylcholine binding site, and there are 2 sites per oligomeric receptor. When incorporated into liposomes or planar li bilaye the nicotinic receptor permits a flux of a, which is promoted... 

If a single gene is cloned in sufficient quantity, it can be sequenced (see Deoxyribonucleic acid) and the amino acid sequence of the gene product can be predicted from the nucleotide sequence of the DNA. For example, the amino acid sequences of the insulin receptor, nicotinic and muscarinic cholinergic acetylcholine receptors, epidermal growth factor precursor and many (thousands) other proteins have been predicted in this way. 

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