|Entry||Database: PDB / ID: 5iou|
|Title||Cryo-EM structure of GluN1/GluN2B NMDA receptor in the glutamate/glycine-bound conformation|
|Keywords||SIGNALING PROTEIN / ligand-gated ion channel / synaptic transmission|
|Function / homology||Calmodulin-binding domain C0, NMDA receptor, NR1 subunit / Glutamate [NMDA] receptor, epsilon subunit, C-terminal / 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 / Ionotropic glutamate receptor ...Calmodulin-binding domain C0, NMDA receptor, NR1 subunit / Glutamate [NMDA] receptor, epsilon subunit, C-terminal / 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 / Ionotropic glutamate receptor / Ionotropic glutamate receptor, metazoa / Receptor, ligand binding region / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / response to magnesium ion / protein heterotetramerization / response to zinc ion / postsynaptic membrane / cell junction / integral component of plasma membrane / metal ion binding / Glutamate receptor ionotropic, NMDA 1 / Glutamate receptor ionotropic, NMDA 2B / Glutamate receptor ionotropic, NMDA 1|
Function and homology information
|Specimen source||Xenopus laevis (African clawed frog)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 7 Å resolution|
|Authors||Zhu, S. / Stein, A.R. / Yoshioka, C. / Lee, C.H. / Goehring, A. / Mchaourab, S.H. / Gouaux, E.|
|Citation||Journal: Cell / Year: 2016|
Title: Mechanism of NMDA Receptor Inhibition and Activation.
Authors: Shujia Zhu / Richard A Stein / Craig Yoshioka / Chia-Hsueh Lee / April Goehring / Hassane S Mchaourab / Eric Gouaux
Abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly ...N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly implicated in diseases ranging from seizure to ischemia. Despite its fundamental importance, little is known about how the NMDAR transitions between inactive and active states and how small molecules inhibit or activate ion channel gating. Here, we report electron cryo-microscopy structures of the GluN1-GluN2B NMDA receptor in an ensemble of competitive antagonist-bound states, an agonist-bound form, and a state bound with agonists and the allosteric inhibitor Ro25-6981. Together with double electron-electron resonance experiments, we show how competitive antagonists rupture the ligand binding domain (LBD) gating "ring," how agonists retain the ring in a dimer-of-dimers configuration, and how allosteric inhibitors, acting within the amino terminal domain, further stabilize the LBD layer. These studies illuminate how the LBD gating ring is fundamental to signal transduction and gating in NMDARs.
SummaryFull reportAbout validation report
|Date||Deposition: Mar 9, 2016 / Release: Apr 20, 2016|
|Structure viewer||Molecule: |
Downloads & links
A: N-methyl-D-aspartate receptor subunit NR1-8a
C: N-methyl-D-aspartate receptor subunit NR1-8a
B: Ionotropic glutamate receptor subunit NR2B
D: Ionotropic glutamate receptor subunit NR2B
Mass: 92651.234 Da / Num. of mol.: 2
Mutation: K51F, R52F, N300Q, N350Q, N368D, N440D, N469D, K493A, K494A, E495A, G610R, I617L, D656R, N769E
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Homo sapiens (human) / References: UniProt: C0KD18, UniProt: A0A1L8F5J9*PLUS
Mass: 93234.742 Da / Num. of mol.: 2
Mutation: M20S, G21R, C22A, A64E, N69Q, N343D, T490V, V615L, E654R, E655R
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: NR2B / Production host: Homo sapiens (human) / References: UniProt: A7XY94
|#3: Chemical||#4: Chemical|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: GluN1-GluN2B NMDA receptor / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: 1,||Source (natural)||Organism: Xenopus laevis (African clawed frog)||Source (recombinant)||Organism: Homo sapiens (human) / Plasmid: unknown||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: OTHER|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 4000 nm / Nominal defocus min: 2500 nm / Cs: 2 mm|
|Specimen holder||Cryogen: NITROGEN|
|Image recording||Average exposure time: 8 sec. / Electron dose: 8.7 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|Image scans||Movie frames/image: 40|
|EM software||Name: RELION / Version: 1.3 / Category: 3D reconstruction|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Particle selection||Number of particles selected: 185009|
|Symmetry||Point symmetry: C1|
|3D reconstruction||Resolution: 7 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 116968 / Symmetry type: POINT|
|Least-squares process||Highest resolution: 7 Å|
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