+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human GluN1-2A with IgG 003-102 WT conformation | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | Channel / heterotetramer / receptor / antibody / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() glycine-gated cation channel activity / excitatory chemical synaptic transmission / directional locomotion / serotonin metabolic process / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / sleep / response to glycine / propylene metabolic process / regulation of monoatomic cation transmembrane transport ...glycine-gated cation channel activity / excitatory chemical synaptic transmission / directional locomotion / serotonin metabolic process / Synaptic adhesion-like molecules / protein localization to postsynaptic membrane / sleep / response to glycine / propylene metabolic process / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / neurotransmitter receptor complex / NMDA selective glutamate receptor complex / Neurexins and neuroligins / ligand-gated sodium channel activity / glutamate binding / glutamate receptor signaling pathway / calcium ion transmembrane import into cytosol / protein heterotetramerization / glycine binding / startle response / positive regulation of reactive oxygen species biosynthetic process / monoatomic cation transmembrane transport / Negative regulation of NMDA receptor-mediated neuronal transmission / dopamine metabolic process / Unblocking of NMDA receptors, glutamate binding and activation / positive regulation of calcium ion transport into cytosol / Long-term potentiation / monoatomic cation transport / excitatory synapse / positive regulation of excitatory postsynaptic potential / monoatomic ion channel complex / regulation of neuronal synaptic plasticity / synaptic cleft / calcium ion homeostasis / MECP2 regulates neuronal receptors and channels / glutamate-gated calcium ion channel activity / neurogenesis / EPHB-mediated forward signaling / sensory perception of pain / sodium ion transmembrane transport / response to amphetamine / ionotropic glutamate receptor signaling pathway / Ras activation upon Ca2+ influx through NMDA receptor / positive regulation of synaptic transmission, glutamatergic / cytoplasmic vesicle membrane / excitatory postsynaptic potential / regulation of membrane potential / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / protein catabolic process / postsynaptic density membrane / brain development / negative regulation of protein catabolic process / visual learning / calcium ion transmembrane transport / regulation of synaptic plasticity / response to wounding / long-term synaptic potentiation / memory / terminal bouton / synaptic vesicle / signaling receptor activity / amyloid-beta binding / presynaptic membrane / RAF/MAP kinase cascade / response to ethanol / chemical synaptic transmission / dendritic spine / postsynaptic membrane / learning or memory / calmodulin binding / neuron projection / postsynaptic density / positive regulation of apoptotic process / response to xenobiotic stimulus / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / glutamatergic synapse / cell surface / positive regulation of transcription by RNA polymerase II / zinc ion binding / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.84 Å | |||||||||
![]() | Michalski K / Furukawa H | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 230.1 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 23.9 KB 23.9 KB | Display Display | ![]() |
Images | ![]() | 88.7 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
Others | ![]() ![]() | 226.9 MB 226.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 16 KB | Display | |
Data in CIF | ![]() | 19 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8vurMC ![]() 8vuhC ![]() 8vujC ![]() 8vulC ![]() 8vunC ![]() 8vuqC ![]() 8vusC ![]() 8vutC ![]() 8vuuC ![]() 8vuvC ![]() 8vuyC ![]() 8vvhC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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_43537_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #2
File | emd_43537_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Human GluN1-2A with IgG 003-102 WT conformation
Entire | Name: Human GluN1-2A with IgG 003-102 WT conformation |
---|---|
Components |
|
-Supramolecule #1: Human GluN1-2A with IgG 003-102 WT conformation
Supramolecule | Name: Human GluN1-2A with IgG 003-102 WT conformation / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() |
-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: ![]() |
Molecular weight | Theoretical: 91.68075 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: VNIGAVLSTR KHEQMFREAV NQANKRHGSW KIQLNATSVT HKPNAIQMAL SVCEDLISSQ VYAILVSHPP TPNDHFTPTP VSYTAGFYR IPVLGLTTRM SIYSDKSIHL SFLRTVPPYS HQSSVWFEMM RVYSWNHIIL LVSDDHEGRA AQKRLETLLE E RESKAEKV ...String: VNIGAVLSTR KHEQMFREAV NQANKRHGSW KIQLNATSVT HKPNAIQMAL SVCEDLISSQ VYAILVSHPP TPNDHFTPTP VSYTAGFYR IPVLGLTTRM SIYSDKSIHL SFLRTVPPYS HQSSVWFEMM RVYSWNHIIL LVSDDHEGRA AQKRLETLLE E RESKAEKV LQFDPGTKNV TALLMEAKEL EARVIILSAS EDDAATVYRA AAMLNMTGSG YVWLVGEREI SGNALRYAPD GI LGLQLIN GKNESAHISD AVGVVAQAVH ELLEKENITD PPRGCVGNTN IWKTGPLFKR VLMSSKYADG VTGRVEFNED GDR KFANYS IMNLQNRKLV QVGIYNGTHV IPNDRKIIWP GGETEKPRGY QMSTRLKIVT IHQEPFVYVK PTLSDGTCKE EFTV NGDPV KKVICTGPND TSPGSPRHTV PQCCYGFCID LLIKLARTMN FTYEVHLVAD GKFGTQERVN NSNKKEWNGM MGELL SGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI LVKKEIPRST LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPF GRF KVNSEEEEED ALTLSSAMWF SWGVLLNSGI GEGAPRSFSA RILGMVWAGF AMIIVASYTA NLAAFLVLDR PEERITG IN DPRLRNPSDK FIYATVKQSS VDIYFRRQVE LSTMYRHMEK HNYESAAEAI QAVRDNKLHA FIWDSAVLEF EASQKCDL V TTGELFFRSG FGIGMRKDSP WKQNVSLSIL KSHENGFMED LDKTWVRYQE CDSRSNAPAT LTFENMAGVF MLVAGGIVA GIFLIFIEIA YKRHK UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 2A
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2A / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 90.684805 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: LNIAVMLGHS HDVTERELRT LWGPEQAAGL PLDVNVVALL MNRTDPKSLI THVCDLMSGA RIHGLVFGDD TDQEAVAQML DFISSHTFV PILGIHGGAS MIMADKDPTS TFFQFGASIQ QQATVMLKIM QDYDWHVFSL VTTIFPGYRE FISFVKTTVD N SFVGWDMQ ...String: LNIAVMLGHS HDVTERELRT LWGPEQAAGL PLDVNVVALL MNRTDPKSLI THVCDLMSGA RIHGLVFGDD TDQEAVAQML DFISSHTFV PILGIHGGAS MIMADKDPTS TFFQFGASIQ QQATVMLKIM QDYDWHVFSL VTTIFPGYRE FISFVKTTVD N SFVGWDMQ NVITLDTSFE DAKTQVQLKK IHSSVILLYC SKDEAVLILS EARSLGLTGY DFFWIVPSLV SGNTELIPKE FP SGLISVS YDDWDYSLEA RVRDGIGILT TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF TEE GYQVHP RLVVIVLNKD REWEKVGKWE NHTLSLRHAV WPRYKSFSDC EPDDNHLSIV TLEEAPFVIV EDIDPLTETC VRNT VPCRK FVKINNSTNE GMNVKKCCKG FCIDILKKLS RTVKFTYDLY LVTNGKHGKK VNNVWNGMIG EVVYQRAVMA VGSLT INEE RSEVVDFSVP FVETGISVMV SRSNGTVSPS AFLEPFSASV WVMMFVMLLI VSAIAVFVFE YFSPVGYNRC LADGRE PGG PSFTIGKAIW LLWGLVFNNS VPVQNPKGTT SKIMVSVWAF FAVIFLASYT ANLAAFMIQE EFVDQVTGLS DKKFQRP HD YSPPFRFGTV PNGSTERNIR NNYPYMHQYM TKFNQKGVED ALVSLKTGKL DAFIYDAAVL NYKAGRDEGC KLVTIGSG Y IFATTGYGIA LQKGSPWKRQ IDLALLQFVG DGEMEELETL WLTGICHNEK NEVMSSQLDI DNMAGVFYML AAAMALSLI TFIWEHLF UniProtKB: Glutamate receptor ionotropic, NMDA 2A |
-Macromolecule #3: Glutamate receptor ionotropic, NMDA 1
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 1 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 91.737867 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: VNIGAVLSTR KHEQMFREAV NQANKRHASW KIQLNATSVT HKPNAIQMAL SVCEDLISSQ VYAILVSHPP TPNDHFTPTP VSYTAGFYR IPVLGLTTRM SIYSDKSIHL SFLRTVPPYS HQSSVWFEMM RVYSWNHIIL LVSDDHEGRA AQKRLETLLE E RESKAEKV ...String: VNIGAVLSTR KHEQMFREAV NQANKRHASW KIQLNATSVT HKPNAIQMAL SVCEDLISSQ VYAILVSHPP TPNDHFTPTP VSYTAGFYR IPVLGLTTRM SIYSDKSIHL SFLRTVPPYS HQSSVWFEMM RVYSWNHIIL LVSDDHEGRA AQKRLETLLE E RESKAEKV LQFDPGTKNV TALLMEAKEL EARVIILSAS EDDAATVYRA AAMLNMTGSG YVWLVGEREI SGNALRYAPD GI LGLQLIN GKNESAHISD AVGVVAQAVH ELLEKENITD PPRGCVGNTN IWKTGPLFKR VLMSSKYADG VTGRVEFNED GDR KFANYS IMNLQRRKLV QVGIYNGTHV IPNDRKIIWP GGETEKPRGY QMSTRLKIVT IHQEPFVYVK PTLSDGTCKE EFTV NGDPV KKVICTGPND TSPGSPRHTV PQCCYGFCID LLIKLARTMN FTYEVHLVAD GKFGTQERVN NSNKKEWNGM MGELL SGQA DMIVAPLTIN NERAQYIEFS KPFKYQGLTI LVKKEIPRST LDSFMQPFQS TLWLLVGLSV HVVAVMLYLL DRFSPF GRF KVNSEEEEED ALTLSSAMWF SWGVLLNSGI GEGAPRSFSA RILGMVWAGF AMIIVASYTA NLAAFLVLDR PEERITG IN DPRLRNPSDK FIYATVKQSS VDIYFRRQVE LSTMYRHMEK HNYESAAEAI QAVRDNKLHA FIWDSAVLEF EASQKCDL V TTGELFFRSG FGIGMRKDSP WKQNVSLSIL KSHENGFMED LDKTWVRYQE CDSRSNAPAT LTFENMAGVF MLVAGGIVA GIFLIFIEIA YKRHK UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #4: 003-102 Heavy
Macromolecule | Name: 003-102 Heavy / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 25.338205 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: LQLQESGPGL VKPSQTLSLT CTVSGGSISS SNWWSWVRQP PGKGLEWIGE IYHSGNTNYN PSLKSRVTVS VDKSKNQFSL KLTSVTAAD TAVYYCARDV SGGVNWFDPW GQGTLVTVLQ LQESGPGLVK PSQTLSLTCT VSGGSISSSN WWSWVRQPPG K GLEWIGEI ...String: LQLQESGPGL VKPSQTLSLT CTVSGGSISS SNWWSWVRQP PGKGLEWIGE IYHSGNTNYN PSLKSRVTVS VDKSKNQFSL KLTSVTAAD TAVYYCARDV SGGVNWFDPW GQGTLVTVLQ LQESGPGLVK PSQTLSLTCT VSGGSISSSN WWSWVRQPPG K GLEWIGEI YHSGNTNYNP SLKSRVTVSV DKSKNQFSLK LTSVTAADTA VYYCARDVSG GVNWFDPWGQ GTLVTV |
-Macromolecule #5: 003-102 Light
Macromolecule | Name: 003-102 Light / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 23.345229 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: NFMLTQPHSV SESPGKTVTI SCTRSSGSIA SNYVQWYQQR PGSAPTTVIY EDNQRPSGVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDSSTV VFGGGTKLTV NFMLTQPHSV SESPGKTVTI SCTRSSGSIA SNYVQWYQQR PGSAPTTVIY E DNQRPSGV ...String: NFMLTQPHSV SESPGKTVTI SCTRSSGSIA SNYVQWYQQR PGSAPTTVIY EDNQRPSGVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDSSTV VFGGGTKLTV NFMLTQPHSV SESPGKTVTI SCTRSSGSIA SNYVQWYQQR PGSAPTTVIY E DNQRPSGV PDRFSGSIDS SSNSASLTIS GLKTEDEADY YCQSYDSSTV VFGGGTKLTV |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | 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: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |