Differential regulation of receptor activation and agonist selectivity by highly conserved tryptophans in the nicotinic acetylcholine receptor binding site.

ABSTRACT: We have shown previously that a highly conserved Tyr in the nicotinic acetylcholine receptor (nAChR) ligand-binding domain (LBD) (alpha7 Tyr188 or alpha4 Tyr195) differentially regulates the activity of acetylcholine (ACh) and the alpha7-selective agonist 3-(4-hydroxy,2-methoxybenzylidene)anabaseine (4OH-GTS-21) in alpha4beta2 and alpha7 nAChR. In this study, we mutated two highly conserved LBD Trp residues in human alpha7 and alpha4beta2 and expressed the receptors in Xenopus laevis oocytes. Alpha7 receptors with Trp55 mutated to Gly or Tyr became less responsive to 4OH-GTS-21, whereas mutation of the homologous Trp57 in beta2 to Gly, Tyr, Phe, or Ala resulted in alpha4beta2 receptors that showed increased responses to 4OH-GTS-21. Mutation of alpha7 Trp55 to Val resulted in receptors for

SUBMITTER: Williams DK 

PROVIDER: S-EPMC2700159 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature