N-terminal domains in the NR2 subunit control desensitization of NMDA receptors

Neuron. 1998 Feb;20(2):317-27. doi: 10.1016/s0896-6273(00)80459-6.


Recent molecular studies of glutamate channels have provided increasingly detailed models of the agonist-binding site and of the channel pore. However, little information is available on the domains involved in channel gating. We examined the molecular determinants for the NR2-subunit specificity of glycine-independent desensitization of NMDA channels using NR2C/NR2A chimeric subunits expressed in HEK 293 cells. We show that glycine-independent desensitization is controlled by N-terminal domains of the NR2 subunit that flank the putative agonist-binding domain: a four amino acid (aa) segment immediately preceding the first transmembrane domain (M1) and a region containing the leucine/isoleucine/valine-binding protein-like (LIVBP-like) domain. Our results provide evidence for a functional role of the region containing the LIVBP-like domain in glutamate receptor channels. We suggest that the pre-M1 segment, presumably situated near the entrance to the pore, serves as a dynamic link between ligand binding and channel gating.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cells, Cultured
  • Cloning, Molecular
  • Electrophysiology
  • Excitatory Amino Acid Agonists / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • Glycine / metabolism
  • Glycine / pharmacology
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Kidney / cytology
  • Ligands
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sensitivity and Specificity


  • Excitatory Amino Acid Agonists
  • Ligands
  • Receptors, N-Methyl-D-Aspartate
  • Glycine

Associated data

  • GENBANK/D13211
  • GENBANK/D13212
  • GENBANK/U08261