Models of the extracellular domain of the nicotinic receptors and of agonist- and Ca2+-binding sites.

ABSTRACT: We constructed a three-dimensional model of the amino-terminal extracellular domain of three major types of nicotinic acetylcholine receptor, (alpha7)5, (alpha4)2(beta2)3, and (alpha1)2beta1gammadelta, on the basis of the recent x-ray structure determination of the molluscan acetylcholine-binding protein. Comparative analysis of the three models reveals that the agonist-binding pocket is much more conserved than the overall structure. Differences exist, however, in the side chains of several residues. In particular, a phenylalanine residue, present in beta2 but not in alpha7, is proposed to contribute to the high affinity for agonists in receptors containing the beta2 subunit. The semiautomatic docking of agonists in the ligand-binding pocket of (alpha7)5 led to positions consistent with l

SUBMITTER: Le Novere N 

PROVIDER: S-EPMC122498 | biostudies-literature | 2002 Mar

REPOSITORIES: biostudies-literature