title: N-terminal domains in the NR2 subunit control desensitization of NMDA receptors.
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) 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.
authors.affiliation: Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Krupp
authors.forename: B
authors.initials: B
authors.lastname: Vissel
authors.forename: S F
authors.initials: SF
authors.lastname: Heinemann
authors.forename: G L
authors.initials: GL
authors.lastname: Westbrook
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D008024:Ligands; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine