+
Open data
-
Basic information
| Entry | Database: PDB / ID: 8vuy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | Rat GluN1-2B with Fab 003-102 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Components |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Keywords | MEMBRANE PROTEIN / Channel / heterotetramer / receptor / antibody | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationcellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / cellular response to curcumin / regulation of cAMP/PKA signal transduction / pons maturation / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / regulation of cell communication / auditory behavior ...cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / cellular response to curcumin / regulation of cAMP/PKA signal transduction / pons maturation / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / regulation of cell communication / auditory behavior / positive regulation of Schwann cell migration / sensitization / olfactory learning / response to hydrogen sulfide / response to other organism / dendritic branch / fear response / conditioned taste aversion / response to methylmercury / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / apical dendrite / regulation of respiratory gaseous exchange / response to manganese ion / transmitter-gated monoatomic ion channel activity / suckling behavior / interleukin-1 receptor binding / positive regulation of inhibitory postsynaptic potential / response to carbohydrate / cellular response to dsRNA / cellular response to lipid / propylene metabolic process / response to glycine / RAF/MAP kinase cascade / negative regulation of dendritic spine maintenance / response to amine / response to growth hormone / heterocyclic compound binding / neurotransmitter receptor complex / Synaptic adhesion-like molecules / response to glycoside / positive regulation of glutamate secretion / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / voltage-gated monoatomic cation channel activity / NMDA selective glutamate receptor complex / glutamate binding / ligand-gated sodium channel activity / neuromuscular process / regulation of axonogenesis / calcium ion transmembrane import into cytosol / response to morphine / regulation of dendrite morphogenesis / male mating behavior / protein heterotetramerization / regulation of synapse assembly / small molecule binding / glycine binding / receptor clustering / startle response / positive regulation of reactive oxygen species biosynthetic process / parallel fiber to Purkinje cell synapse / regulation of MAPK cascade / behavioral response to pain / monoatomic ion channel complex / regulation of postsynaptic membrane potential / monoatomic cation transmembrane transport / response to electrical stimulus / action potential / extracellularly glutamate-gated ion channel activity / response to magnesium ion / positive regulation of calcium ion transport into cytosol / cellular response to glycine / associative learning / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / regulation of neuronal synaptic plasticity / monoatomic cation transport / glutamate receptor binding / prepulse inhibition / detection of mechanical stimulus involved in sensory perception of pain / social behavior / ligand-gated monoatomic ion channel activity / response to mechanical stimulus / neuron development / multicellular organismal response to stress / long-term memory / phosphatase binding / postsynaptic density, intracellular component / behavioral fear response / response to fungicide / monoatomic cation channel activity / synaptic cleft / calcium ion homeostasis / positive regulation of synaptic transmission, glutamatergic / cellular response to manganese ion / glutamate-gated receptor activity / regulation of long-term synaptic depression / D2 dopamine receptor binding / glutamate-gated calcium ion channel activity Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | ![]() Homo sapiens (human) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.81 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Michalski, K. / Furukawa, H. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | United States, 1items
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Citation | Journal: Nat Struct Mol Biol / Year: 2024Title: Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis. Authors: Kevin Michalski / Taha Abdulla / Sam Kleeman / Lars Schmidl / Ricardo Gómez / Noriko Simorowski / Francesca Vallese / Harald Prüss / Manfred Heckmann / Christian Geis / Hiro Furukawa / ![]() Abstract: Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) ...Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most dominant autoimmune encephalitis; however, insights into how autoantibodies recognize and alter receptor functions remain limited. Here we determined structures of human and rat NMDARs bound to three distinct patient-derived antibodies using single-particle electron cryo-microscopy. These antibodies bind different regions within the amino-terminal domain of the GluN1 subunit. Through electrophysiology, we show that all three autoantibodies acutely and directly reduced NMDAR channel functions in primary neurons. Antibodies show different stoichiometry of binding and antibody-receptor complex formation, which in one antibody, 003-102, also results in reduced synaptic localization of NMDARs. These studies demonstrate mechanisms of diverse epitope recognition and direct channel regulation of anti-NMDAR autoantibodies underlying autoimmune encephalitis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| History |
|
-
Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
|---|
-
Downloads & links
-
Download
| PDBx/mmCIF format | 8vuy.cif.gz | 625.2 KB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb8vuy.ent.gz | 490.6 KB | Display | PDB format |
| PDBx/mmJSON format | 8vuy.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vu/8vuy ftp://data.pdbj.org/pub/pdb/validation_reports/vu/8vuy | HTTPS FTP |
|---|
-Related structure data
| Related structure data | ![]() 43544MC ![]() 8vuhC ![]() 8vujC ![]() 8vulC ![]() 8vunC ![]() 8vuqC ![]() 8vurC ![]() 8vusC ![]() 8vutC ![]() 8vuuC ![]() 8vuvC ![]() 8vvhC M: map data used to model this data C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
Components
| #1: Protein | Mass: 91944.094 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Protein | Mass: 91269.125 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #3: Antibody | Mass: 12477.862 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)#4: Antibody | Mass: 11582.475 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)Has protein modification | Y | |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: Rat GluN1-2B with Fab 003-102 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
|---|---|
| Molecular weight | Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 7.5 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
|---|---|
| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
| Electron lens | Mode: OTHER / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
| Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
| EM software |
| ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 516895 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
|
Movie
Controller
About Yorodumi





Homo sapiens (human)
United States, 1items
Citation























PDBj








FIELD EMISSION GUN