Identification of residues in the adult nicotinic acetylcholine receptor that confer selectivity for curariform antagonists

Nina Bren, Steven M. Sine

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

We identify residues in the ε and δ subunits of the adult nicotinic acetylcholine receptor that give the αε and αδ binding sites different affinities for the curariform antagonist dimethyl d-tubocurarine (DMT). By constructing ε-δ subunit chimeras, coexpressing them with complementary subunits, and measuring DMT binding, we identify two pairs of residues, Ile(ε58)/His(δ60) and Asp(ε59)/Ala(δ61), responsible for DMT site selectivity in the adult receptor. The two determinants contribute approximately equally to the binding site and interact in contributing to the site. Exchange of these residues from one subunit to the other exchanges the affinities of the resulting binding sites. These determinants in the adult receptor are far from those that confer site selectivity in the fetal receptor; determinants in the fetal receptor are Ile(γ116)/Val(δ118), Tyr(γ117)/Thr(δ119), and Ser(γ161/Lys(δ163). Thus, alternative residues confer DMT selectivity in fetal and adult acetylcholine receptors.

Original languageEnglish (US)
Pages (from-to)30793-30798
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number49
DOIs
StatePublished - Dec 5 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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