Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines

Neuron. 1996 Aug;17(2):343-52. doi: 10.1016/s0896-6273(00)80165-8.


The structure of the NMDA receptor channel M2 segment was investigated by probing the extracellular and cytoplasmic faces of cysteine-substituted NR1-NR2C channels with charged sulfhydryl-specific reagents. The pattern of accessible positions suggests that the M2 segment forms a channel-lining loop originating and ending on the cytoplasmic side of the channel, with the ascending limb in an alpha-helical structure and the descending limb in an extended structure. A functionally critical asparagine (N-site) is positioned at the tip of the loop, and a cluster of hydrophilic residues of the descending limb, adjacent to the tip, forms the narrow constriction of the channel. An apparent asymmetric positioning of the NR1- and NR2-subunit N-site asparagines may account for their unequal role in Ca2+ permeability and Mg2+ block.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cysteine / chemistry*
  • Cysteine / genetics*
  • Cytoplasm / chemistry
  • Ethyl Methanesulfonate / analogs & derivatives
  • Ethyl Methanesulfonate / pharmacology
  • Extracellular Space / chemistry
  • Female
  • Indicators and Reagents / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Mutation / physiology
  • Oocytes / physiology
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Xenopus laevis


  • Indicators and Reagents
  • Membrane Proteins
  • Receptors, N-Methyl-D-Aspartate
  • methanethiosulfonate ethylammonium
  • Ethyl Methanesulfonate
  • Cysteine