title: Conformational changes at the agonist binding domain of the N-methyl-D-aspartic acid receptor.
abstract: The conformational changes in the agonist binding domain of the glycine-binding GluN1 and glutamate-binding GluN2A subunits of the N-methyl D-aspartic acid receptor upon binding agonists of varying efficacy have been investigated by luminescence resonance energy transfer (LRET) measurements. The LRET-based distances indicate a cleft closure conformational change at the GluN1 subunit upon binding agonists; however, no significant changes in the cleft closure are observed between partial and full agonists. This is consistent with the previously reported crystal structures for the isolated agonist binding domain of this receptor. Additionally, the LRET-based distances show that the agonist binding domain of the glutamate-binding GluN2A subunit exhibits a graded cleft closure with the extent of cleft closure being proportional to the extent of activation, indicating that the mechanism of activation in this subunit is similar to that of the glutamate binding α-amino-5-methyl-3-hydroxy-4-isoxazole propionate and kainate subtypes of the ionotropic glutamate receptors.
authors: Center for Membrane Biology, Department of Biochemistry and Molecular Biology, Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Texas 77030, USA.
authors: Anu
authors: A
authors: Rambhadran
authors: Jennifer
authors: J
authors: Gonzalez
authors: Vasanthi
authors: V
authors: Jayaraman
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000494:pharmacology; D006860:Hydrogen Bonding; D008958:Models, Molecular; D018377:Neurotransmitter Agents / Q000737:chemistry; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D011487:Protein Conformation; D018092:Kainic Acid Receptors / Q000737:chemistry; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry*; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid