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Science 1 May 1987:
Vol. 236. no. 4801, pp. 600 - 605
DOI: 10.1126/science.3107123
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Articles

Science, Vol 236, Issue 4801, 600-605
Copyright © 1987 by American Association for the Advancement of Science

articles

Primary structure and biochemical properties of an M2 muscarinic receptor

EG Peralta, JW Winslow, GL Peterson, DH Smith, A Ashkenazi, J Ramachandran, MI Schimerlik, and DJ Capon

A partial amino acid sequence obtained for porcine atrial muscarinic acetylcholine receptor was used to isolate complementary DNA clones containing the complete receptor coding region. The deduced 466-amino acid polypeptide exhibits extensive structural and sequence homology with other receptors coupled to guanine nucleotide binding (G) proteins (for example, the beta-adrenergic receptor and rhodopsins); this similarity predicts a structure of seven membrane-spanning regions distinguished by the disposition of a large cytoplasmic domain. Stable transfection of the Chinese hamster ovary cell line with the atrial receptor complementary DNA leads to the binding of muscarinic antagonists in these cells with affinities characteristic of the M2 receptor subtype. The atrial muscarinic receptor is encoded by a unique gene consisting of a single coding exon and multiple, alternatively spliced 5' noncoding regions. The atrial receptor is distinct from the cerebral muscarinic receptor gene product, sharing only 38% overall amino acid homology and possessing a completely nonhomologous large cytoplasmic domain, suggesting a role for the latter region in differential effector coupling.


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