Hulme E C, Birdsall N J, Wheatley M, Curtis C, Pedder E K, Poyner D, Stockton J M, Eveleigh P
Division of Physical Biochemistry, National Institute for Medical Research, Mill Hill, London, UK.
Postgrad Med J. 1987;63 Suppl 1:5-12.
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 beta-adrenergic receptor.
对纯化的大鼠前脑毒蕈碱型乙酰胆碱受体（mAChR）的结构和结合研究与该受体在结构上类似于视紫红质的观点一致。我们提出它由一个短的、糖基化的N端组成，接着是七个跨膜螺旋，由膜外环连接。跨膜螺旋构成了分子的很大一部分。两种肽，其中一种是糖基化的，因此靠近分子的N端部分，被不可逆拮抗剂[3H]-PrBCM标记在酸性残基上，因此可能构成配体结合位点的一部分。mAChR的构象灵活性，以及因此其结合刚性选择性配体如哌仑西平的能力，受到关键半胱氨酸残基氧化状态的强烈影响。该分子被认为在细胞质C端尾部终止，它与细胞质环一起参与对GTP结合蛋白的识别。C端易受蛋白水解攻击，并显示出与β-肾上腺素能受体C端序列同源的证据。
