Covalent trapping of methyllycaconitine at the α4-α4 interface of the α4α2 nicotinic acetylcholine receptor: Antagonist binding site and mode of receptor inhibition revealed

Nathan L. Absalom, Gracia Quek, Trevor M. Lewis, Taima Qudah, Ida Von Arenstorff, Joseph I. Ambrus, Kasper Harpsøe, Nasiara Karim, Thomas Balle, Malcolm D. McLeod, Mary Chebib*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    Background: Methyllycaconitine is an antagonist at subtypes of the nicotinic acetylcholine receptor. Results: A reactive methyllycaconitine probe was covalently trapped by a cysteine introduced on the complementary face of the α4 subunit and only in the (α4)3(β2)2 nAChR stoichiometry. Conclusion: The α4-α4 interface on the α4β2 nAChR contains a methyllycaconitine binding site. Significance: Defining the molecular interactions of nAChR ligands at the α4-α interface may lead to superior therapeutics.

    Original languageEnglish
    Pages (from-to)26521-26532
    Number of pages12
    JournalJournal of Biological Chemistry
    Volume288
    Issue number37
    DOIs
    Publication statusPublished - 13 Sept 2013

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