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Basic information
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| Title | Rat GluN1-2B with Fab 003-102 | |||||||||
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Keywords | Channel / heterotetramer / receptor / antibody / MEMBRANE PROTEIN | |||||||||
| 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 / positive regulation of Schwann cell migration / regulation of cell communication ...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 / positive regulation of Schwann cell migration / regulation of cell communication / auditory behavior / sensitization / olfactory learning / response to methylmercury / response to other organism / response to hydrogen sulfide / fear response / dendritic branch / conditioned taste aversion / protein localization to postsynaptic membrane / regulation of ARF protein signal transduction / apical dendrite / suckling behavior / transmitter-gated monoatomic ion channel activity / response to manganese ion / interleukin-1 receptor binding / response to carbohydrate / regulation of respiratory gaseous exchange / cellular response to lipid / propylene metabolic process / response to glycine / response to growth hormone / cellular response to dsRNA / RAF/MAP kinase cascade / negative regulation of dendritic spine maintenance / positive regulation of inhibitory postsynaptic potential / neurotransmitter receptor complex / heterocyclic compound binding / response to amine / Synaptic adhesion-like molecules / response to glycoside / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / glutamate binding / voltage-gated monoatomic cation channel activity / neuromuscular process / ligand-gated sodium channel activity / regulation of axonogenesis / calcium ion transmembrane import into cytosol / response to morphine / positive regulation of glutamate secretion / male mating behavior / regulation of dendrite morphogenesis / protein heterotetramerization / positive regulation of reactive oxygen species biosynthetic process / regulation of synapse assembly / small molecule binding / glycine binding / startle response / receptor clustering / parallel fiber to Purkinje cell synapse / regulation of neuronal synaptic plasticity / regulation of MAPK cascade / regulation of postsynaptic membrane potential / associative learning / behavioral response to pain / positive regulation of calcium ion transport into cytosol / extracellularly glutamate-gated ion channel activity / cellular response to glycine / response to electrical stimulus / positive regulation of dendritic spine maintenance / action potential / monoatomic cation transmembrane transport / multicellular organismal response to stress / response to magnesium ion / Unblocking of NMDA receptors, glutamate binding and activation / neuron development / detection of mechanical stimulus involved in sensory perception of pain / monoatomic cation transport / glutamate receptor binding / response to mechanical stimulus / social behavior / ligand-gated monoatomic ion channel activity / behavioral fear response / prepulse inhibition / phosphatase binding / long-term memory / postsynaptic density, intracellular component / calcium ion homeostasis / synaptic cleft / response to fungicide / monoatomic cation channel activity / adult locomotory behavior / cellular response to manganese ion / glutamate-gated receptor activity / regulation of long-term synaptic depression / positive regulation of synaptic transmission, glutamatergic / glutamate-gated calcium ion channel activity / presynaptic active zone membrane Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.81 Å | |||||||||
Authors | Michalski K / Furukawa H | |||||||||
| Funding support | United States, 1 items
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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. | |||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_43544.map.gz | 230 MB | EMDB map data format | |
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| Header (meta data) | emd-43544-v30.xml emd-43544.xml | 21.8 KB 21.8 KB | Display Display | EMDB header |
| Images | emd_43544.png | 75.1 KB | ||
| Filedesc metadata | emd-43544.cif.gz | 7.2 KB | ||
| Others | emd_43544_half_map_1.map.gz emd_43544_half_map_2.map.gz | 226.5 MB 226.5 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-43544 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-43544 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 8vuyMC ![]() 8vuhC ![]() 8vujC ![]() 8vulC ![]() 8vunC ![]() 8vuqC ![]() 8vurC ![]() 8vusC ![]() 8vutC ![]() 8vuuC ![]() 8vuvC ![]() 8vvhC 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_43544.map.gz / Format: CCP4 / Size: 244.1 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: 0.856 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: #1
| File | emd_43544_half_map_1.map | ||||||||||||
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-Half map: #2
| File | emd_43544_half_map_2.map | ||||||||||||
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Sample components
-Entire : Rat GluN1-2B with Fab 003-102
| Entire | Name: Rat GluN1-2B with Fab 003-102 |
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| Components |
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-Supramolecule #1: Rat GluN1-2B with Fab 003-102
| Supramolecule | Name: Rat GluN1-2B with Fab 003-102 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| 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: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 91.944094 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: KIVNIGAVLS TRKHEQMFRE AVNQANKRHG SWKIQLQATS VTHKPNAIQM ALSVCEDLIS SQVYAILVSH PPTPNDHFTP TPVSYTAGF YRIPVLGLTT RMSIYSDKSI HLSFLRTVPP YSHQSSVWFE MMRVYNWNHI ILLVSDDHEG RAAQKRLETL L EERESKAE ...String: KIVNIGAVLS TRKHEQMFRE AVNQANKRHG SWKIQLQATS VTHKPNAIQM ALSVCEDLIS SQVYAILVSH PPTPNDHFTP TPVSYTAGF YRIPVLGLTT RMSIYSDKSI HLSFLRTVPP YSHQSSVWFE MMRVYNWNHI ILLVSDDHEG RAAQKRLETL L EERESKAE KVLQFDPGTK NVTALLMEAR ELEARVIILS ASEDDAATVY RAAAMLDMTG SGYVWLVGER EISGNALRYA PD GIIGLQL INGKNESAHI SDAVGVVAQA VHELLEKENI TDPPRGCVGN TNIWKTGPLF KRVLMSSKYA DGVTGRVEFN EDG DRKFAQ YSIMNLQNRK LVQVGIYNGT HVIPNDRKII WPGGETEKPR GYQMSTRLKI VTIHQEPFVY VKPTMSDGTC KEEF TVNGD PVKKVICTGP NDTSPGSPRH TVPQCCYGFC IDLLIKLART MQFTYEVHLV ADGKFGTQER VQNSNKKEWN GMMGE LLSG QADMIVAPLT INNERAQYIE FSKPFKYQGL TILVKKEIPR STLDSFMNPF QSTLWLLVGL SVHVVAVMLY LLDRFS PFG RFKVNSEEEE EDALTLSSAM WFSWGVLLNS GIGEGAPRSF SARILGMVWA GFAMIIVASY TANLAAFLVL DRPEERI TG INDPRLRNPS DKFIYATVKQ SSVDIYFRRQ VELSTMYRHM EKHNYESAAE AIQAVRDNKL HAFIWDSAVL EFEASQKC D LVTTGELFFR SGFGIGMRKD SPWKQQVSLS ILKSHENGFM EDLDKTWVRY QECDSRSNAP ATLTFENMAG VFMIVAGGI VAGIFLIFIE IAYKSRA UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 2B
| Macromolecule | Name: Glutamate receptor ionotropic, NMDA 2B / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 91.269125 KDa |
| Recombinant expression | Organism: ![]() |
| Sequence | String: SIGIAVILVG TSDEVAIKDA HEKDDFHHLS VVPRVELVAM NETDPKSIIT RICDLMSDRK IQGVVFADDT DQEAIAQILD FISAQTLTP ILGIHGGSSM IMADKDESSM FFQFGPSIEQ QASVMLNIME EYDWYIFSIV TTYFPGYQDF VNKIRSTIEN S FVGWELEE ...String: SIGIAVILVG TSDEVAIKDA HEKDDFHHLS VVPRVELVAM NETDPKSIIT RICDLMSDRK IQGVVFADDT DQEAIAQILD FISAQTLTP ILGIHGGSSM IMADKDESSM FFQFGPSIEQ QASVMLNIME EYDWYIFSIV TTYFPGYQDF VNKIRSTIEN S FVGWELEE VLLLDMSLDD GDSKIQNQLK KLQSPIILLY CTKEEATYIF EVANSVGLTG YGYTWIVPSL VAGDTDTVPS EF PTGLISV SYDEWDYGLP ARVRDGIAII TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRDLS FSE EGYQMH PKLVIILLNK ERKWERVGKW KDKSLQMKYY VWPRMCPETE EQEDDHLSIV TLEEAPFVIV ESVDPLSGTC MRNT VPCEK RIISENKTDE EPGYIKKCCK GFCIDILKKI SKSVKFTYDL YLVTNGKHGK KINGTWNGMI GEVVMKRAYM AVGSL TINE ERSEVVDFSV PFIETGISVM VSRSNGTVSP SAFLEPFSAD VWVMMFVMLL IVSAVAVFVF EYFSPVGYNR CLADGR EPG GPSFTIGKAI WLLWGLVFNN SVPVQNPKGT TSKIMVSVWA FFAVIFLASY TANLAAFMIQ EEYVDQVSGL SDKKFQR PN DFSPPFRFGT VPNGSTERNI RNNYAEMHAY MGKFNQRGVD DALLSLKTGK LDAFIYDAAV LNYMAGRDEG CKLVTIGS G KVFASTGYGI AIQKDSGWKR QVDLAILQLF GDGEMEELEA LWLTGICHNE KNEVMSSQLD IDNMAGVFYM LGAAMALSL ITFISEHLFY WQ UniProtKB: Glutamate receptor ionotropic, NMDA 2B |
-Macromolecule #3: 003-102 Heavy
| Macromolecule | Name: 003-102 Heavy / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 12.477862 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: LQLQESGPGL VKPSQTLSLT CTVSGGSISS SNWWSWVRQP PGKGLEWIGE IYHSGNTNYN PSLKSRVTVS VDKSKNQFSL KLTSVTAAD TAVYYCARDV SGGVNWFDPW GQGTLV |
-Macromolecule #4: 003-102 Light
| Macromolecule | Name: 003-102 Light / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 11.582475 KDa |
| Recombinant expression | Organism: Homo sapiens (human) |
| Sequence | String: NFMLTQPHSV SESPGKTVTI SCTRSSGSIA SNYVQWYQQR PGSAPTTVIY EDNQRPSGVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDSSTV VFGGGTKLT |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Buffer | pH: 7.5 |
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| Vitrification | Cryogen name: ETHANE |
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Electron microscopy
| Microscope | FEI TITAN KRIOS |
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| 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 / 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 |
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About Yorodumi




Keywords
Homo sapiens (human)
Authors
United States, 1 items
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Processing
FIELD EMISSION GUN
