Structural and binding studies on the purified rat forebrain muscarinic acetylcholine receptor (mAChR) are consistent with the idea that the receptor is structurally analogous to rhodopsin. We propose that it consists of a short, glycosylated N-terminus, followed by seven transmembrane helices, joined by extra-membranous loops. The transmembrane helices make up a substantial proportion of the molecule. Two peptides, one of which is glycosylated, and therefore close to the N-terminal part of the molecule are labelled on acidic residues by the irreversible antagonist [3H]-PrBCM, and may thus form part of the ligand binding site. The conformational flexibility of the mAChR, and hence its ability to bind rigid selective ligands such as pirenzepine is strongly affected by the oxidation state of key cysteine residues. The molecule is proposed to terminate in a cytoplasmic C-terminal tail, which participates, together with the cytoplasmic loops, in the recognition of GTP-binding proteins. The C-terminus is susceptible to proteolytic attack, and shows evidence of sequence homology to the C-terminus of the β-adrenergic receptor.
|Number of pages||8|
|Journal||Postgraduate Medical Journal|
|Issue number||SUPPL. 1|
|Publication status||Published - 1987|
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