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Yorodumi- EMDB-72080: Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), ... -
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Basic information
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| Title | Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), glycine and glutamate-bound state | |||||||||
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Keywords | ligand-gated ion channel / NMDA / antibody / native / TRANSPORT PROTEIN | |||||||||
| Function / homology | Function and homology informationAssembly and cell surface presentation of NMDA receptors / Synaptic adhesion-like molecules / EPHB-mediated forward signaling / Unblocking of NMDA receptors, glutamate binding and activation / neurotransmitter receptor transport, plasma membrane to endosome / RAF/MAP kinase cascade / receptor recycling / directional locomotion / pons maturation / regulation of cell communication ...Assembly and cell surface presentation of NMDA receptors / Synaptic adhesion-like molecules / EPHB-mediated forward signaling / Unblocking of NMDA receptors, glutamate binding and activation / neurotransmitter receptor transport, plasma membrane to endosome / RAF/MAP kinase cascade / receptor recycling / directional locomotion / pons maturation / regulation of cell communication / positive regulation of Schwann cell migration / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / serotonin metabolic process / regulation of ARF protein signal transduction / transmitter-gated monoatomic ion channel activity / suckling behavior / positive regulation of inhibitory postsynaptic potential / sleep / propylene metabolic process / response to glycine / locomotion / dendritic spine organization / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / voltage-gated monoatomic cation channel activity / glutamate binding / neurotransmitter receptor complex / ligand-gated sodium channel activity / glutamate receptor signaling pathway / regulation of axonogenesis / calcium ion transmembrane import into cytosol / neuromuscular process / transport vesicle membrane / response to morphine / regulation of dendrite morphogenesis / protein heterotetramerization / male mating behavior / regulation of synapse assembly / glycine binding / startle response / ligand-gated monoatomic ion channel activity / cellular response to zinc ion / positive regulation of reactive oxygen species biosynthetic process / dopamine metabolic process / parallel fiber to Purkinje cell synapse / response to lithium ion / monoatomic cation transmembrane transport / monoatomic ion channel complex / positive regulation of calcium ion transport into cytosol / regulation of postsynaptic membrane potential / action potential / modulation of excitatory postsynaptic potential / associative learning / positive regulation of dendritic spine maintenance / regulation of neuronal synaptic plasticity / social behavior / positive regulation of protein targeting to membrane / monoatomic cation transport / glutamate receptor binding / prepulse inhibition / long-term memory / phosphatase binding / positive regulation of synaptic transmission, glutamatergic / postsynaptic density, intracellular component / monoatomic cation channel activity / synaptic cleft / calcium ion homeostasis / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / neurogenesis / presynaptic active zone membrane / cell adhesion molecule binding / dendrite membrane / ionotropic glutamate receptor binding / excitatory synapse / sensory perception of pain / ionotropic glutamate receptor signaling pathway / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / regulation of neuron apoptotic process / protein tyrosine kinase binding / synaptic membrane / cytoplasmic vesicle membrane / positive regulation of excitatory postsynaptic potential / sodium ion transmembrane transport / hippocampal mossy fiber to CA3 synapse / response to amphetamine / learning / adult locomotory behavior / excitatory postsynaptic potential / regulation of membrane potential / synaptic transmission, glutamatergic / cellular response to amino acid stimulus / locomotory behavior / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of long-term neuronal synaptic plasticity Similarity search - Function | |||||||||
| Biological species | ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 6.14 Å | |||||||||
Authors | Kim J / Gouaux E | |||||||||
| Funding support | United States, 1 items
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Citation | Journal: Sci Adv / Year: 2026Title: Cryo-EM of autoantibody-bound NMDA receptors reveals antigenic hotspots in an active immunization model of anti-NMDAR encephalitis. Authors: Junhoe Kim / Farzad Jalali-Yazdi / Brian E Jones / Gary L Westbrook / Eric Gouaux / ![]() Abstract: Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti--methyl-d-aspartate receptor (NMDAR) ...Autoantibodies targeting synaptic membrane proteins are associated with autoimmune encephalitis manifested by seizures, psychosis, and memory dysfunction. Anti--methyl-d-aspartate receptor (NMDAR) encephalitis, a prototype of these autoimmune synaptic disorders, is unexpectedly common. Unfortunately, how the native repertoire of anti-NMDAR autoantibodies recognizes NMDARs and the precise locations of antigenic epitopes remain poorly understood. Here, we used an active immunization model that closely mimics the human disease to immunize adult mice with intact GluN1/GluN2A receptors, resulting in fulminant autoimmune encephalitis. Serum was collected at 6 weeks postimmunization for single-particle cryo-electron microscopy of GluN1/GluN2A receptors complexed with purified polyclonal anti-NMDAR autoantibody fragments. Native autoantibodies recognized two distinct binding sites on the GluN1 amino-terminal domain, which we confirmed using monoclonal antibodies bound to native NMDARs purified from mouse brain. Structural analysis of autoantibody-bound NMDAR complexes identified antigenic hotspots within the GluN1 amino-terminal domain. These hotspots provide potential targets for therapeutic intervention. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_72080.map.gz | 21.6 MB | EMDB map data format | |
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| Header (meta data) | emd-72080-v30.xml emd-72080.xml | 31.6 KB 31.6 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_72080_fsc.xml | 7.4 KB | Display | FSC data file |
| Images | emd_72080.png | 21.2 KB | ||
| Filedesc metadata | emd-72080.cif.gz | 8.9 KB | ||
| Others | emd_72080_additional_1.map.gz emd_72080_additional_2.map.gz emd_72080_half_map_1.map.gz emd_72080_half_map_2.map.gz | 40.5 MB 38.2 MB 39.8 MB 39.8 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-72080 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-72080 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9pztMC ![]() 9pzqC ![]() 9pzrC ![]() 9pzsC ![]() 9pzuC ![]() 9pzvC ![]() 9pzwC ![]() 9pzxC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_72080.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 2.091 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Additional map: sharpen map
| File | emd_72080_additional_1.map | ||||||||||||
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| Annotation | sharpen map | ||||||||||||
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| Density Histograms |
-Additional map: processed in C2 symmetry
| File | emd_72080_additional_2.map | ||||||||||||
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| Annotation | processed in C2 symmetry | ||||||||||||
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-Half map: #2
| File | emd_72080_half_map_1.map | ||||||||||||
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-Half map: #1
| File | emd_72080_half_map_2.map | ||||||||||||
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Sample components
-Entire : Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), ...
| Entire | Name: Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), glycine and glutamate-bound state |
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| Components |
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-Supramolecule #1: Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), ...
| Supramolecule | Name: Native GluN1/GluN2A in complex with 5F11 and 3D2 Fabs (class 3), glycine and glutamate-bound state type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 717 KDa |
-Macromolecule #1: Heavy chain of GluN2A-specific monoclonal Fab fragment, termed 3D2
| Macromolecule | Name: Heavy chain of GluN2A-specific monoclonal Fab fragment, termed 3D2 type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 15.448522 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MVSAIVLYVL LAAAAHSAFA QVQLQQSGAE LMKPGASVKI SCKATGYTFR SYWIEWLKQR PGHGLEWIGE ILPGSGRTNY NEKFKGKAT ITADTSSNTA YMQLSSLTSE DSAVYYCTRS RGTMITREFT YWGQGALVTV SA |
-Macromolecule #2: Light chain of GluN2A-specific monoclonal Fab fragment, termed 3D2
| Macromolecule | Name: Light chain of GluN2A-specific monoclonal Fab fragment, termed 3D2 type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 13.989831 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MVSAIVLYVL LAAAAHSAFA DIVLTQSPAS LAVSLGQRAT ISCRASESVE YYGTTLMQWY QQKPGQPPKL LIYAASNVDS GVPARFSGS GSGTDFSLNI HPVEEDDIAM YFCQQSRKVP STFGGGTKLE IK |
-Macromolecule #3: Glutamate receptor ionotropic, NMDA 2A
| Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2A / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 165.619891 KDa |
| Sequence | String: MGRLGYWTLL VLPALLVWHG PAQNAAAEKG TPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH ...String: MGRLGYWTLL VLPALLVWHG PAQNAAAEKG TPALNIAVLL GHSHDVTERE LRNLWGPEQA TGLPLDVNVV ALLMNRTDPK SLITHVCDL MSGARIHGLV FGDDTDQEAV AQMLDFISSQ TFIPILGIHG GASMIMADKD PTSTFFQFGA SIQQQATVML K IMQDYDWH VFSLVTTIFP GYRDFISFIK TTVDNSFVGW DMQNVITLDT SFEDAKTQVQ LKKIHSSVIL LYCSKDEAVL IL SEARSLG LTGYDFFWIV PSLVSGNTEL IPKEFPSGLI SVSYDDWDYS LEARVRDGLG ILTTAASSML EKFSYIPEAK ASC YGQTEK PETPLHTLHQ FMVNVTWDGK DLSFTEEGYQ VHPRLVVIVL NKDREWEKVG KWENQTLSLR HAVWPRYKSF SDCE PDDNH LSIVTLEEAP FVIVEDIDPL TETCVRNTVP CRKFVKINNS TNEGMNVKKC CKGFCIDILK KLSRTVKFTY DLYLV TNGK HGKKVNNVWN GMIGEVVYQR AVMAVGSLTI NEERSEVVDF SVPFVETGIS VMVSRSNGTV SPSAFLEPFS ASVWVM MFV MLLIVSAIAV FVFEYFSPVG YNRNLAKGKA PHGPSFTIGK AIWLLWGLVF NNSVPVQNPK GTTSKIMVSV WAFFAVI FL ASYTANLAAF MIQEEFVDQV TGLSDKKFQR PHDYSPPFRF GTVPNGSTER NIRNNYPYMH QYMTKFNQRG VEDALVSL K TGKLDAFIYD AAVLNYKAGR DEGCKLVTIG SGYIFATTGY GIALQKGSPW KRQIDLALLQ FVGDGEMEEL ETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIWEHL FYWKLRFCFT GVCSDRPGLL FSISRGIYSC IHGVHIEEKK KSPDFNLTG SQSNMLKLLR SAKNISNMSN MNSSRMDSPK RAADFIQRGS LIVDMVSDKG NLIYSDNRSF QGKDSIFGEN M NELQTFVA NRHKDSLSNY VFQGQHPLTL NESNPNTVEV AVSTESKGNS RPRQLWKKSM ESLRQDSLNQ NPVSQRDEKT AE NRTHSLK SPRYLPEEVA HSDISETSSR ATCHREPDNN KNHKTKDNFK RSMASKYPKD CSEVERTYVK TKASSPRDKI YTI DGEKEP SFHLDPPQFI ENIVLPENVD FPDTYQDHNE NFRKGDSTLP MNRNPLHNED GLPNNDQYKL YAKHFTLKDK GSPH SEGSD RYRQNSTHCR SCLSNLPTYS GHFTMRSPFK CDACLRMGNL YDIDEDQMLQ ETGNPATREE AYQQDWSQNN ALQFQ KNKL KINRQHSYDN ILDKPREIDL SRPSRSISLK DRERLLEGNL YGSLFSVPSS KLLGNKSSLF PQGLEDSKRS KSLLPD HTS DNPFLHTYGD DQRLVIGRCP SDPYKHSLPS QAVNDSYLRS SLRSTASYCS RDSRGHSDVY ISEHVMPYAA NKNNMYS TP RVLNSCSNRR VYKKMPSIES DV UniProtKB: Glutamate receptor ionotropic, NMDA 2A |
-Macromolecule #4: Glutamate receptor ionotropic, NMDA 1
| Macromolecule | Name: Glutamate receptor ionotropic, NMDA 1 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 105.61782 KDa |
| Sequence | String: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS ...String: MSTMHLLTFA LLFSCSFARA ACDPKIVNIG AVLSTRKHEQ MFREAVNQAN KRHGSWKIQL NATSVTHKPN AIQMALSVCE DLISSQVYA ILVSHPPTPN DHFTPTPVSY TAGFYRIPVL GLTTRMSIYS DKSIHLSFLR TVPPYSHQSS VWFEMMRVYN W NHIILLVS DDHEGRAAQK RLETLLEERE SKAEKVLQFD PGTKNVTALL MEARDLEARV IILSASEDDA ATVYRAAAML NM TGSGYVW LVGEREISGN ALRYAPDGII GLQLINGKNE SAHISDAVGV VAQAVHELLE KENITDPPRG CVGNTNIWKT GPL FKRVLM SSKYADGVTG RVEFNEDGDR KFANYSIMNL QNRKLVQVGI YNGTHVIPND RKIIWPGGET EKPRGYQMST RLKI VTIHQ EPFVYVKPTM SDGTCKEEFT VNGDPVKKVI CTGPNDTSPG SPRHTVPQCC YGFCVDLLIK LARTMNFTYE VHLVA DGKF GTQERVNNSN KKEWNGMMGE LLSGQADMIV APLTINNERA QYIEFSKPFK YQGLTILVKK EIPRSTLDSF MQPFQS TLW LLVGLSVHVV AVMLYLLDRF SPFGRFKVNS EEEEEDALTL SSAMWFSWGV LLNSGIGEGA PRSFSARILG MVWAGFA MI IVASYTANLA AFLVLDRPEE RITGINDPRL RNPSDKFIYA TVKQSSVDIY FRRQVELSTM YRHMEKHNYE SAAEAIQA V RDNKLHAFIW DSAVLEFEAS QKCDLVTTGE LFFRSGFGIG MRKDSPWKQN VSLSILKSHE NGFMEDLDKT WVRYQECDS RSNAPATLTF ENMAGVFMLV AGGIVAGIFL IFIEIAYKRH KDARRKQMQL AFAAVNVWRK NLQDRKSGRA EPDPKKKATF RAITSTLAS SFKRRRSSKD TSTGGGRGAL QNQKDTVLPR RAIEREEGQL QLCSRHRES UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #5: Heavy chain of GluN1-specific monoclonal Fab fragment, termed 5F11
| Macromolecule | Name: Heavy chain of GluN1-specific monoclonal Fab fragment, termed 5F11 type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 29.432527 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MVSAIVLYVL LAAAAHSAFA QGQMQQSGAE LVKPGASVKL SCKTSGFSFS TSYINWLKQK PGQSLEWIAW IYAGTDGTSY NQKFTDKAQ LTVDTSSSTA YMQFSSLTTD DSAIYYCARE GIYYGNYAGF TYWGQGTLVT VSAAKTTPPS VYPLAPGSAA Q TNSMVTLG ...String: MVSAIVLYVL LAAAAHSAFA QGQMQQSGAE LVKPGASVKL SCKTSGFSFS TSYINWLKQK PGQSLEWIAW IYAGTDGTSY NQKFTDKAQ LTVDTSSSTA YMQFSSLTTD DSAIYYCARE GIYYGNYAGF TYWGQGTLVT VSAAKTTPPS VYPLAPGSAA Q TNSMVTLG CLVKGYFPEP VTVTWNSGSL SSGVHTFPAV LQSDLYTLSS SVTVPSSTWP SETVTCNVAH PASSTKVDKK LV PRGSAAA AGTGSGGGDY KDHDGDYKDH DIDYKDDDDK |
-Macromolecule #6: Light chain of GluN1-specific monoclonal Fab fragment, termed 5F11
| Macromolecule | Name: Light chain of GluN1-specific monoclonal Fab fragment, termed 5F11 type: protein_or_peptide / ID: 6 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 26.909961 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: MVSAIVLYVL LAAAAHSAFA DIVMTQSPSS LAVTAGEKVT MRCKSSQSLL WSVNQNNYLS WYQQKQGQPP KLLIYGASIR ESWVPDRFT GSGSGTDFTL TISNVHAEDL AVYYCQHNHG SFLPYTFGGG TKLEIKRADA APTVSIFPPS SEQLTSGGAS V VCFLNNFY ...String: MVSAIVLYVL LAAAAHSAFA DIVMTQSPSS LAVTAGEKVT MRCKSSQSLL WSVNQNNYLS WYQQKQGQPP KLLIYGASIR ESWVPDRFT GSGSGTDFTL TISNVHAEDL AVYYCQHNHG SFLPYTFGGG TKLEIKRADA APTVSIFPPS SEQLTSGGAS V VCFLNNFY PKDINVKWKI DGSERQNGVL NSWTDQDSKD STYSMSSTLT LTKDEYERHN SYTCEATHKT STSPIVKSFN RN ECSN |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 0.05 mg/mL |
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| Buffer | pH: 8 |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 290 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
| Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number real images: 9851 / Average electron dose: 65.0 e/Å2 |
| Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.0 µm |
| Sample stage | Cooling holder cryogen: NITROGEN |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Keywords
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN

