Structures of the M2 channel-lining segments from nicotinic acetylcholine and NMDA receptors by NMR spectroscopy

Nat Struct Biol. 1999 Apr;6(4):374-9. doi: 10.1038/7610.


The structures of functional peptides corresponding to the predicted channel-lining M2 segments of the nicotinic acetylcholine receptor (AChR) and of a glutamate receptor of the NMDA subtype (NMDAR) were determined using solution NMR experiments on micelle samples, and solid-state NMR experiments on bilayer samples. Both M2 segments form straight transmembrane alpha-helices with no kinks. The AChR M2 peptide inserts in the lipid bilayer at an angle of 12 degrees relative to the bilayer normal, with a rotation about the helix long axis such that the polar residues face the N-terminal side of the membrane, which is assigned to be intracellular. A model built from these solid-state NMR data, and assuming a symmetric pentameric arrangement of M2 helices, results in a funnel-like architecture for the channel, with the wide opening on the N-terminal intracellular side.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Escherichia coli / genetics
  • Ion Channel Gating
  • Ion Channels / chemistry*
  • Isotope Labeling
  • Lipid Bilayers
  • Lipids / chemistry
  • Magnetic Resonance Spectroscopy / methods
  • Micelles
  • Models, Chemical
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Protein Conformation
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Nicotinic / chemistry*
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Solutions


  • Ion Channels
  • Lipid Bilayers
  • Lipids
  • Micelles
  • Peptide Fragments
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic
  • Recombinant Proteins
  • Solutions

Associated data

  • PDB/1A11
  • PDB/1CEK
  • PDB/2NR1