|Entry||Database: PDB / ID: 5uow|
|Title||Triheteromeric NMDA receptor GluN1/GluN2A/GluN2B in complex with glycine, glutamate, MK-801 and a GluN2B-specific Fab, at pH 6.5|
|Keywords||MEMBRANE PROTEIN / membrane protein|
|Function / homology||Ionotropic glutamate receptor, metazoa / Receptor, ligand binding region / Ligated ion channel L-glutamate- and glycine-binding site / N-methyl D-aspartate receptor 2B3 C-terminus / Calmodulin-binding domain C0 of NMDA receptor NR1 subunit / Receptor family ligand binding region / Ligand-gated ion channel / Periplasmic binding protein-like I / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Glutamate [NMDA] receptor, epsilon subunit, C-terminal ...Ionotropic glutamate receptor, metazoa / Receptor, ligand binding region / Ligated ion channel L-glutamate- and glycine-binding site / N-methyl D-aspartate receptor 2B3 C-terminus / Calmodulin-binding domain C0 of NMDA receptor NR1 subunit / Receptor family ligand binding region / Ligand-gated ion channel / Periplasmic binding protein-like I / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Glutamate [NMDA] receptor, epsilon subunit, C-terminal / Calmodulin-binding domain C0, NMDA receptor, NR1 subunit / Ionotropic glutamate receptor / calcium ion transmembrane import into cytosol / glutamate-gated calcium ion channel activity / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / response to magnesium ion / extracellularly glutamate-gated ion channel activity / protein heterotetramerization / response to zinc ion / postsynaptic membrane / cell junction / intracellular / integral component of plasma membrane / metal ion binding / Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2B / Glutamate receptor ionotropic, NMDA 2A / Glutamate receptor ionotropic, NMDA 1|
Function and homology information
|Specimen source||Xenopus laevis (African clawed frog)|
Mus musculus (house mouse)
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 4.5 Å resolution|
|Authors||Lu, W. / Du, J. / Goehring, A. / Gouaux, E.|
|Citation||Journal: Science / Year: 2017|
Title: Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation.
Authors: Wei Lü / Juan Du / April Goehring / Eric Gouaux
Abstract: -methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B ...-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino-terminal domains (ATDs) adopt "closed" and "open" clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo-2-fold-related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity.
SummaryFull reportAbout validation report
|Date||Deposition: Feb 1, 2017 / Release: Mar 22, 2017|
|Structure viewer||Molecule: |
Downloads & links
A: N-methyl-D-aspartate receptor subunit NR1-8a
B: N-methyl-D-aspartate receptor subunit NR2A
C: N-methyl-D-aspartate receptor subunit NR1-8a
D: Ionotropic glutamate receptor subunit NR2B
F: GluN2B-specific Fab, termed 11D1
G: GluN2B-specific Fab, termed 11D1
-N-methyl-D-aspartate receptor subunit ... , 2 types, 3 molecules A
Mass: 91639.867 Da / Num. of mol.: 2 / Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Homo sapiens (human) / References: UniProt: C0KD18, UniProt: A0A1L8F5J9*PLUS
Mass: 93664.344 Da / Num. of mol.: 1 / Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: LOC100127346 / Production host: Homo sapiens (human) / References: UniProt: B7ZSK1
-Protein/peptide , 2 types, 3 molecules D
|#3: Protein/peptide|| |
Mass: 94552.234 Da / Num. of mol.: 1 / Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: NR2B / Production host: Homo sapiens (human) / References: UniProt: A7XY94
Mass: 18400.619 Da / Num. of mol.: 2 / Source: (gene. exp.) Mus musculus (house mouse) / Production host: Homo sapiens (human)
-Non-polymers , 3 types, 18 molecules
|#6: Chemical|| ChemComp-GLU / ||#7: Chemical|| ChemComp-BMK / (|
|Sequence details||Sample sequence for this chains is unknown|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: membrane protein / Type: COMPLEX / Entity ID: 1,||Source (natural)||Organism: Xenopus laevis (African clawed frog)||Source (recombinant)||Organism: Homo sapiens (human)||Buffer solution||pH: 6.5||Specimen||Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES||Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 0.84 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|3D reconstruction||Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 302052 / Symmetry type: POINT|
|Least-squares process||Highest resolution: 4.5 Å|
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