Nicotinic acetylcholine receptor-lipid interactions: Mechanistic insight and biological function

Biochimica Et Biophysica Acta
John E BaenzigerJiayin Sun

Abstract

Membrane lipids are potent modulators of the nicotinic acetylcholine receptor (nAChR) from Torpedo. Lipids influence nAChR function by both conformational selection and kinetic mechanisms, stabilizing varying proportions of activatable versus non-activatable conformations, as well as influencing the transitions between these conformational states. Of note, some membranes stabilize an electrically silent uncoupled conformation that binds agonist but does not undergo agonist-induced conformational transitions. The uncoupled nAChR, however, does transition to activatable conformations in relatively thick lipid bilayers, such as those found in lipid rafts. In this review, we discuss current understanding of lipid-nAChR interactions in the context of increasingly available high resolution structural and functional data. These data highlight different sites of lipid action, including the lipid-exposed M4 transmembrane α-helix. Current evidence suggests that lipids alter nAChR function by modulating interactions between M4 and the adjacent transmembrane α-helices, M1 and M3. These interactions have also been implicated in both the folding and trafficking of nAChRs to the cell surface. We review current mechanistic understanding of lip...Continue Reading

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Citations

Jan 8, 2016·Pflügers Archiv : European journal of physiology·Jarred M Whitlock, H Criss Hartzell
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Nov 18, 2020·Nature Chemical Biology·Mackenzie J Thompson, John E Baenziger
Apr 21, 2020·Biochimica Et Biophysica Acta. Biomembranes·Mackenzie J Thompson, John E Baenziger
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