Optochemical control of genetically engineered neuronal nicotinic acetylcholine receptors

Ivan Tochitsky, Matthew R. Banghart, Alexandre Mourot, Jennifer Z. Yao, Benjamin Gaub, Richard H. Kramer, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

Advances in synthetic chemistry, structural biology, molecular modelling and molecular cloning have enabled the systematic functional manipulation of transmembrane proteins. By combining genetically manipulated proteins with light-sensitive ligands, innately 'blind' neurobiological receptors can be converted into photoreceptors, which allows them to be photoregulated with high spatiotemporal precision. Here, we present the optochemical control of neuronal nicotinic acetylcholine receptors (nAChRs) with photoswitchable tethered agonists and antagonists. Using structure-based design, we produced heteromeric α3β4 and α4β2 nAChRs that can be activated or inhibited with deep-violet light, but respond normally to acetylcholine in the dark. The generation of these engineered receptors should facilitate investigation of the physiological and pathological functions of neuronal nAChRs and open a general pathway to photosensitizing pentameric ligand-gated ion channels.

Original languageEnglish (US)
Pages (from-to)105-111
Number of pages7
JournalNature chemistry
Volume4
Issue number2
DOIs
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Tochitsky, I., Banghart, M. R., Mourot, A., Yao, J. Z., Gaub, B., Kramer, R. H., & Trauner, D. (2012). Optochemical control of genetically engineered neuronal nicotinic acetylcholine receptors. Nature chemistry, 4(2), 105-111. https://doi.org/10.1038/nchem.1234