Identification of residues in the neuronal α7 acetylcholine receptor that confer selectivity for conotoxin ImI

Polly A. Quiram, Steven M. Sine

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


To identify residues in the neuronal α7 acetylcholine subunit that confer high affinity for the neuronal-specific toxin conotoxin ImI (CTx ImI), we constructed α71 chimeras containing segments of the muscle α1 subunit inserted into equivalent positions of the neuronal α7 subunit. To achieve high expression in 293 human embryonic kidney cells and formation of homo-oligomers, we joined the extracellular domains of each chimera to the M1 junction of the 5-hydroxytryptamine-3 (5HT-3) subunit. Measurements of CTx ImI binding to the chimeric receptors reveal three pairs of residues in equivalent positions of the primary sequence that confer high affinity of CTx ImI for α7/5HT-3 over α1/5HT-3 homo-oligomers. Two of these pairs, α7Trp551Arg55 and α7Ser591Gln59, are within one of the four loops that contribute to the traditional non-α subunit face of the muscle receptor binding site. The third pair, α7Thr771Lys77, is not within previously described loops of either the α or non-α faces and may represent a new loop or an allosterically coupled loop. Exchanging these residues between α1 and α7 subunits exchanges the affinities of the binding sites for CTx ImI, suggesting that the α7 and α1 subunits, despite sequence identity of only 38%, share similar protein scaffolds.

Original languageEnglish (US)
Pages (from-to)11001-11006
Number of pages6
JournalJournal of Biological Chemistry
Issue number18
StatePublished - May 1 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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