+
Open data
-
Basic information
| Entry | ![]() | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Title | Human GluN1-2B with Fab 007-168 Local refinement of ATD | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | Receptor / antibody / ion channel / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
| Function / homology | Function and homology informationglycine-gated cation channel activity / excitatory chemical synaptic transmission / Activated NTRK2 signals through FYN / Synaptic adhesion-like molecules / response to glycine / propylene metabolic process / negative regulation of dendritic spine maintenance / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity ...glycine-gated cation channel activity / excitatory chemical synaptic transmission / Activated NTRK2 signals through FYN / Synaptic adhesion-like molecules / response to glycine / propylene metabolic process / negative regulation of dendritic spine maintenance / Assembly and cell surface presentation of NMDA receptors / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / Neurexins and neuroligins / glutamate binding / ligand-gated sodium channel activity / neurotransmitter receptor complex / glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / protein heterotetramerization / glycine binding / positive regulation of reactive oxygen species biosynthetic process / monoatomic cation transmembrane transport / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of calcium ion transport into cytosol / Long-term potentiation / excitatory synapse / monoatomic cation transport / regulation of neuronal synaptic plasticity / monoatomic ion channel complex / positive regulation of excitatory postsynaptic potential / synaptic cleft / positive regulation of synaptic transmission, glutamatergic / calcium ion homeostasis / MECP2 regulates neuronal receptors and channels / glutamate-gated calcium ion channel activity / EPHB-mediated forward signaling / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / sodium ion transmembrane transport / ionotropic glutamate receptor signaling pathway / Ras activation upon Ca2+ influx through NMDA receptor / synaptic membrane / regulation of membrane potential / excitatory postsynaptic potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic transmission, glutamatergic / brain development / postsynaptic density membrane / visual learning / regulation of synaptic plasticity / calcium ion transmembrane transport / long-term synaptic potentiation / terminal bouton / synaptic vesicle / late endosome / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / response to ethanol / chemical synaptic transmission / dendritic spine / postsynaptic membrane / learning or memory / cytoskeleton / calmodulin binding / lysosome / neuron projection / postsynaptic density / dendrite / calcium ion binding / synapse / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.69 Å | |||||||||
Authors | Michalski K / Furukawa H | |||||||||
| Funding support | United States, 1 items
| |||||||||
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
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Map data | emd_43541.map.gz | 286.2 MB | EMDB map data format | |
|---|---|---|---|---|
| Header (meta data) | emd-43541-v30.xml emd-43541.xml | 20.9 KB 20.9 KB | Display Display | EMDB header |
| Images | emd_43541.png | 57.8 KB | ||
| Filedesc metadata | emd-43541.cif.gz | 6.8 KB | ||
| Others | emd_43541_half_map_1.map.gz emd_43541_half_map_2.map.gz | 280.5 MB 280.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43541 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43541 | HTTPS FTP |
-Validation report
| Summary document | emd_43541_validation.pdf.gz | 1.1 MB | Display | EMDB validaton report |
|---|---|---|---|---|
| Full document | emd_43541_full_validation.pdf.gz | 1.1 MB | Display | |
| Data in XML | emd_43541_validation.xml.gz | 16.6 KB | Display | |
| Data in CIF | emd_43541_validation.cif.gz | 19.8 KB | Display | |
| Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43541 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-43541 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8vuvMC ![]() 8vuhC ![]() 8vujC ![]() 8vulC ![]() 8vunC ![]() 8vuqC ![]() 8vurC ![]() 8vusC ![]() 8vutC ![]() 8vuuC ![]() 8vuyC ![]() 8vvhC M: atomic model generated by this map C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
| File | Download / File: emd_43541.map.gz / Format: CCP4 / Size: 303.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.856 Å | ||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
|
-Supplemental data
-Half map: #1
| File | emd_43541_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #2
| File | emd_43541_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-
Sample components
-Entire : Human GluN1-2B with Fab 007-168 Local refinement of ATD
| Entire | Name: Human GluN1-2B with Fab 007-168 Local refinement of ATD |
|---|---|
| Components |
|
-Supramolecule #1: Human GluN1-2B with Fab 007-168 Local refinement of ATD
| Supramolecule | Name: Human GluN1-2B with Fab 007-168 Local refinement of ATD type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Glutamate receptor ionotropic, NMDA 1
| Macromolecule | Name: Glutamate receptor ionotropic, NMDA 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 41.549199 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: DPKIVNIGAV LSTRKHEQMF REAVNQANKR HGSWKIQLNA TSVTHKPNAI QMALSVCEDL ISSQVYAILV SHPPTPNDHF TPTPVSYTA GFYRIPVLGL TTRMSIYSDK SIHLSFLRTV PPYSHQSSVW FEMMRVYNWN HIILLVSDDH EGRAAQKRLE T LLEERESK ...String: DPKIVNIGAV LSTRKHEQMF REAVNQANKR HGSWKIQLNA TSVTHKPNAI QMALSVCEDL ISSQVYAILV SHPPTPNDHF TPTPVSYTA GFYRIPVLGL TTRMSIYSDK SIHLSFLRTV PPYSHQSSVW FEMMRVYNWN HIILLVSDDH EGRAAQKRLE T LLEERESK AEKVLQFDPG TKNVTALLME ARELEARVII LSASEDDAAT VYRAAAMLNM TGSGYVWLVG EREISGNALR YA PDGIIGL QLINGKNESA HISDAVGVVA QAVHELLEKE NITDPPRGCV GNTNIWKTGP LFKRVLMSSK YADGVTGRVE FNE DGDRKF AQYSIMNLQN RKLVQVGIYN GTHVIPNDRK IIWPGGETEK PRGYQ UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: 007-168 Heavy
| Macromolecule | Name: 007-168 Heavy / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 22.52225 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: QVQLVQSGAE AKKPGESLKI SCKASGYSFT TFWIGWVRQM PGSGLEWIGI IYPGDSDTRY SPSFQGHVTI SADRSTSTAY LQWSSLKAS DTAMYYCARS AVFDYWGQGT LVTVSSASTK GPSVFPLAPS SGTAALGCLV KDYFPEPVTV SWNSGALTSG V HTFPAVLQ ...String: QVQLVQSGAE AKKPGESLKI SCKASGYSFT TFWIGWVRQM PGSGLEWIGI IYPGDSDTRY SPSFQGHVTI SADRSTSTAY LQWSSLKAS DTAMYYCARS AVFDYWGQGT LVTVSSASTK GPSVFPLAPS SGTAALGCLV KDYFPEPVTV SWNSGALTSG V HTFPAVLQ SSGLYSLSSV VTVPSSSLGT QTYICNVNHK PSNTKVDKKV EPK |
-Macromolecule #3: 007-168 Light
| Macromolecule | Name: 007-168 Light / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 23.455982 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: EIVMTQSPAT LSVSPGGRAT LSCRASQSVS SNLAWYQQKP GQAPRLLIYG ASTRATGIPV RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWPTSWT FGQGTKLEIK RTAAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ ...String: EIVMTQSPAT LSVSPGGRAT LSCRASQSVS SNLAWYQQKP GQAPRLLIYG ASTRATGIPV RFSGSGSGTE FTLTISSLQS EDFAVYYCQ QYNNWPTSWT FGQGTKLEIK RTAAAPSVFI FPPSDEQLKS GTASVVCLLN NFYPREAKVQ WKVDNALQSG N SQESVTEQ DSKDSTYSLS STLTLSKADY EKHKLYACEV THQGLSSPVT KSFNRGE |
-Macromolecule #4: Glutamate receptor ionotropic, NMDA 2B
| Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2B / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 40.358699 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: SAPSIGIAVI LVGTSDEVAI KDAHEKDDFH HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQT LTPILGIHGG SSMIMADKDE SSMFFQFGPS IEQQASVMLN IMEEYDWYIF SIVTTYFPGY QDFVNKIRST I ENSFVGWE ...String: SAPSIGIAVI LVGTSDEVAI KDAHEKDDFH HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQT LTPILGIHGG SSMIMADKDE SSMFFQFGPS IEQQASVMLN IMEEYDWYIF SIVTTYFPGY QDFVNKIRST I ENSFVGWE LEEVLLLDMS LDDGDSKIQN QLKKLQSPII LLYCTKEEAT YIFEVANSVG LTGYGYTWIV PSLVAGDTDT VP SEFPTGL ISVSYDEWDY GLPARVRDGI AIITTAASDM LSEHSFIPEP KSSCYNTHEK RIYQSNMLNR YLINVTFEGR DLS FSEEGY QMHPKLVIIL LNKERKWERV GKWKDKSLQM K UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.5 |
|---|---|
| Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
| Microscope | FEI TITAN KRIOS |
|---|---|
| Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
Movie
Controller
About Yorodumi




Keywords
Homo sapiens (human)
Authors
United States, 1 items
Citation




































Z (Sec.)
Y (Row.)
X (Col.)





































Processing
FIELD EMISSION GUN
