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Open data
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Basic information
Entry | Database: PDB / ID: 8vuy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Title | Rat GluN1-2B with Fab 003-102 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / Channel / heterotetramer / receptor / antibody | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Function / homology | ![]() cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / regulation of cAMP/PKA signal transduction / sensitization / EPHB-mediated forward signaling ...cellular response to curcumin / cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / regulation of cAMP/PKA signal transduction / sensitization / EPHB-mediated forward signaling / auditory behavior / Assembly and cell surface presentation of NMDA receptors / olfactory learning / conditioned taste aversion / dendritic branch / response to hydrogen sulfide / regulation of respiratory gaseous exchange / response to other organism / positive regulation of inhibitory postsynaptic potential / protein localization to postsynaptic membrane / apical dendrite / regulation of ARF protein signal transduction / response to methylmercury / fear response / response to glycine / propylene metabolic process / response to carbohydrate / cellular response to dsRNA / interleukin-1 receptor binding / negative regulation of dendritic spine maintenance / positive regulation of glutamate secretion / cellular response to lipid / response to growth hormone / Synaptic adhesion-like molecules / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / RAF/MAP kinase cascade / voltage-gated monoatomic cation channel activity / response to manganese ion / neurotransmitter receptor complex / transmitter-gated monoatomic ion channel activity / NMDA selective glutamate receptor complex / ligand-gated sodium channel activity / response to morphine / calcium ion transmembrane import into cytosol / glutamate binding / regulation of axonogenesis / neuromuscular process / male mating behavior / regulation of dendrite morphogenesis / protein heterotetramerization / regulation of synapse assembly / heterocyclic compound binding / positive regulation of reactive oxygen species biosynthetic process / glycine binding / parallel fiber to Purkinje cell synapse / receptor clustering / positive regulation of calcium ion transport into cytosol / suckling behavior / response to amine / small molecule binding / startle response / social behavior / monoatomic cation transmembrane transport / associative learning / : / behavioral response to pain / response to magnesium ion / regulation of MAPK cascade / regulation of neuronal synaptic plasticity / cellular response to glycine / extracellularly glutamate-gated ion channel activity / regulation of postsynaptic membrane potential / monoatomic cation transport / excitatory synapse / positive regulation of excitatory postsynaptic potential / action potential / monoatomic ion channel complex / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / long-term memory / cellular response to manganese ion / behavioral fear response / postsynaptic density, intracellular component / glutamate receptor binding / neuron development / synaptic cleft / prepulse inhibition / multicellular organismal response to stress / detection of mechanical stimulus involved in sensory perception of pain / phosphatase binding / monoatomic cation channel activity / response to electrical stimulus / calcium ion homeostasis / glutamate-gated receptor activity / response to mechanical stimulus / response to fungicide / D2 dopamine receptor binding / presynaptic active zone membrane / cell adhesion molecule binding Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.81 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
![]() | Michalski, K. / Furukawa, H. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: 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 |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 625.2 KB | Display | ![]() |
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PDB format | ![]() | 490.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 95.5 KB | Display | |
Data in CIF | ![]() | 149.1 KB | Display | |
Arichive directory | ![]() ![]() | 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 ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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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.) ![]() ![]() #4: Antibody | Mass: 11582.475 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Rat GluN1-2B with Fab 003-102 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
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 |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
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) |
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Processing
EM software |
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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 |
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