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Molecular mechanisms of acetylcholine receptor–lipid interactions: from model membranes to human biology

Abstract

Lipids are potent modulators of the Torpedo nicotinic acetylcholine receptor. Lipids influence nicotinic receptor function by allosteric mechanisms, stabilizing varying proportions of pre-existing resting, open, desensitized, and uncoupled conformations. Recent structures reveal that lipids could alter function by modulating transmembrane α-helix/α-helix packing, which in turn could alter the conformation of the allosteric interface that links the agonist-binding and transmembrane pore domains—this interface is essential in the coupling of agonist binding to channel gating. We discuss potential mechanisms by which lipids stabilize different conformational states in the context of the hypothesis that lipid–nicotinic receptor interactions modulate receptor function at biological synapses.

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Abbreviations

ABD:

Agonist binding domain

nAChR:

Nicotinic acetylcholine receptor

ELIC:

Erwinia ligand-gated ion channel

GLIC:

Gloebacter ligand-gated ion channel

PA:

Phosphatidic acid

TMD:

Transmembrane domain

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Baenziger, J.E., daCosta, C.J.B. Molecular mechanisms of acetylcholine receptor–lipid interactions: from model membranes to human biology. Biophys Rev 5, 1–9 (2013). https://doi.org/10.1007/s12551-012-0078-7

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Keywords

  • Lipid–protein interactions
  • Cys-loop receptors
  • Pentameric ligand-gated ion channels
  • Uncoupled state
  • Lipid rafts
  • Nicotinic receptor trafficking
  • Phospholipase activity
  • Synaptic plasticity