A model of the closed form of the nicotinic acetylcholine receptor m2 channel pore

Biophys J. 2004 Aug;87(2):792-9. doi: 10.1529/biophysj.103.039396.

Abstract

The nicotinic acetylcholine receptor is a neurotransmitter-gated ion channel in the postsynaptic membrane. It is composed of five homologous subunits, each of which contributes one transmembrane helix--the M2 helix--to create the channel pore. The M2 helix from the delta subunit is capable of forming a channel by itself. Although a model of the receptor was recently proposed based on a low-resolution, cryo-electron microscopy density map, we found that the model does not explain much of the other available experimental data. Here we propose a new model of the M2 channel derived solely from helix packing and symmetry constraints. This model agrees well with experimental results from solid-state NMR, chemical reactivity, and mutagenesis experiments. The model depicts the channel pore, the channel gate, and the residues responsible for cation specificity.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Membrane / chemistry*
  • Computer Simulation
  • Ion Channel Gating*
  • Ion Channels / chemistry*
  • Membrane Fluidity*
  • Models, Chemical*
  • Models, Molecular*
  • Porosity
  • Protein Conformation
  • Protein Structure, Secondary
  • Receptors, Nicotinic / chemistry*
  • Structure-Activity Relationship

Substances

  • Ion Channels
  • Receptors, Nicotinic