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

Johannes J. Krupp, Bryce Vissel, Stephen F. Heinemann, Gary Westbrook

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

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) segement immediately preceding the first transmembrance domain (M1) and a region containing the leucine/isoleucin/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.

Original languageEnglish (US)
Pages (from-to)317-327
Number of pages11
JournalNeuron
Volume20
Issue number2
DOIs
StatePublished - Feb 1998

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N-Methyl-D-Aspartate Receptors
Glycine
HEK293 Cells
Glutamate Receptors
Valine
N-Methylaspartate
Leucine
Glutamic Acid
Carrier Proteins
Binding Sites
Ligands
Amino Acids
Protein Domains

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

N-terminal domains in the NR2 subunit control desensitization of NMDA receptors. / Krupp, Johannes J.; Vissel, Bryce; Heinemann, Stephen F.; Westbrook, Gary.

In: Neuron, Vol. 20, No. 2, 02.1998, p. 317-327.

Research output: Contribution to journalArticle

Krupp, Johannes J. ; Vissel, Bryce ; Heinemann, Stephen F. ; Westbrook, Gary. / N-terminal domains in the NR2 subunit control desensitization of NMDA receptors. In: Neuron. 1998 ; Vol. 20, No. 2. pp. 317-327.
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