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Open data
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Basic information
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Title | Glycine-bound GluN1a-3A LBD heterotetramer (local refinement) | |||||||||||||||
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![]() | Channel / receptor / MEMBRANE PROTEIN | |||||||||||||||
Function / homology | ![]() negative regulation of dendritic spine development / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / glutamate receptor activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins ...negative regulation of dendritic spine development / excitatory chemical synaptic transmission / Synaptic adhesion-like molecules / propylene metabolic process / response to glycine / glutamate receptor activity / regulation of monoatomic cation transmembrane transport / Assembly and cell surface presentation of NMDA receptors / NMDA glutamate receptor activity / Neurexins and neuroligins / NMDA selective glutamate receptor complex / calcium ion transmembrane import into cytosol / glutamate binding / positive regulation of reactive oxygen species biosynthetic process / protein heterotetramerization / glycine binding / positive regulation of calcium ion transport into cytosol / Negative regulation of NMDA receptor-mediated neuronal transmission / Unblocking of NMDA receptors, glutamate binding and activation / dendrite development / regulation of neuronal synaptic plasticity / monoatomic cation transmembrane transport / monoatomic cation transport / positive regulation of excitatory postsynaptic potential / Long-term potentiation / ligand-gated monoatomic ion channel activity / excitatory synapse / prepulse inhibition / calcium ion homeostasis / synaptic cleft / glutamate-gated calcium ion channel activity / EPHB-mediated forward signaling / presynaptic modulation of chemical synaptic transmission / Ras activation upon Ca2+ influx through NMDA receptor / ionotropic glutamate receptor signaling pathway / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / excitatory postsynaptic potential / protein phosphatase 2A binding / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / postsynaptic density membrane / visual learning / modulation of chemical synaptic transmission / brain development / calcium channel activity / regulation of synaptic plasticity / terminal bouton / calcium ion transport / rhythmic process / synaptic vesicle / presynapse / signaling receptor activity / amyloid-beta binding / RAF/MAP kinase cascade / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / postsynaptic density / calmodulin binding / neuron projection / neuronal cell body / glutamatergic synapse / synapse / dendrite / calcium ion binding / endoplasmic reticulum membrane / protein-containing complex binding / cell surface / positive regulation of transcription by RNA polymerase II / identical protein binding / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.96 Å | |||||||||||||||
![]() | Michalski K / Furukawa H | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. Authors: Kevin Michalski / Hiro Furukawa / ![]() Abstract: -methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. ...-methyl-d-aspartate receptors (NMDARs) and other ionotropic glutamate receptors (iGluRs) mediate most of the excitatory signaling in the mammalian brains in response to the neurotransmitter glutamate. Uniquely, NMDARs composed of GluN1 and GluN3 are activated exclusively by glycine, the neurotransmitter conventionally mediating inhibitory signaling when it binds to pentameric glycine receptors. The GluN1-3 NMDARs are vital for regulating neuronal excitability, circuit function, and specific behaviors, yet our understanding of their functional mechanism at the molecular level has remained limited. Here, we present cryo-electron microscopy structures of GluN1-3A NMDARs bound to an antagonist, CNQX, and an agonist, glycine. The structures show a 1-3-1-3 subunit heterotetrameric arrangement and an unprecedented pattern of GluN3A subunit orientation shift between the glycine-bound and CNQX-bound structures. Site-directed disruption of the unique subunit interface in the glycine-bound structure mitigated desensitization. Our study provides a foundation for understanding the distinct structural dynamics of GluN3 that are linked to the unique function of GluN1-3 NMDARs. | |||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 230 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.2 KB 15.2 KB | Display Display | ![]() |
Images | ![]() | 71.4 KB | ||
Filedesc metadata | ![]() | 5.5 KB | ||
Others | ![]() ![]() | 226.8 MB 226.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8uueMC ![]() 8uswC ![]() 8usxC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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_42580_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_42580_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Glycine-bound GluN1-3A LBD heterotetramer (local refinement)
Entire | Name: Glycine-bound GluN1-3A LBD heterotetramer (local refinement) |
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Components |
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-Supramolecule #1: Glycine-bound GluN1-3A LBD heterotetramer (local refinement)
Supramolecule | Name: Glycine-bound GluN1-3A LBD heterotetramer (local refinement) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 400 KDa |
-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: 45.902477 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: STRLKIVTIH QEPFVYVKPT MSDGTCKEEF TVNGDPVKKV ICTGPNDTSP GSPRHTVPQC CYGFCIDLLI KLARTMNFTY EVHLVADGK FGTQERVNNS NKKEWNGMMG ELLSGQADMI VAPLTINNER AQYIEFSKPF KYQGLTILVK KEIPRSTLDS F MQPFQSTL ...String: STRLKIVTIH QEPFVYVKPT MSDGTCKEEF TVNGDPVKKV ICTGPNDTSP GSPRHTVPQC CYGFCIDLLI KLARTMNFTY EVHLVADGK FGTQERVNNS NKKEWNGMMG ELLSGQADMI VAPLTINNER AQYIEFSKPF KYQGLTILVK KEIPRSTLDS F MQPFQSTL WLLVGLSVHV VAVMLYLLDR FSPFGRFKVN SEEEEEDALT LSSAMWFSWG VLLNSGIGEG APRSFSARIL GM VWAGFAM IIVASYTANL AAFLVLDRPE ERITGINDPR LRNPSDKFIY ATVKQSSVDI YFRRQVELST MYRHMEKHNY ESA AEAIQA VRDNKLHAFI WDSAVLEFEA SQKCDLVTTG ELFFRSGFGI GMRKDSPWKQ NVSLSILKSH ENGFMEDLDK TWVR YQEC UniProtKB: Glutamate receptor ionotropic, NMDA 1 |
-Macromolecule #2: Glutamate receptor ionotropic, NMDA 3A
Macromolecule | Name: Glutamate receptor ionotropic, NMDA 3A / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 45.53532 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SKLHLRVVTL IEHPFVFTRE VDDEGLCPAG QLCLDPMTND SSTLDSLFSS LHSSNDTVPI KFKKCCYGYC IDLLEKIAED MNFDFDLYI VGDGKYGAWK NGHWTGLVGD LLRGTAHMAV TSFSINTARS QVIDFTSPFF STSLGILVRT RDTAAPIGAF M WPLHWTMW ...String: SKLHLRVVTL IEHPFVFTRE VDDEGLCPAG QLCLDPMTND SSTLDSLFSS LHSSNDTVPI KFKKCCYGYC IDLLEKIAED MNFDFDLYI VGDGKYGAWK NGHWTGLVGD LLRGTAHMAV TSFSINTARS QVIDFTSPFF STSLGILVRT RDTAAPIGAF M WPLHWTMW LGIFVALHIT AVFLTLYEWK SPFGLTPKGR NRSKVFSFSS ALNICYALLF GRTVAIKPPK CWTGRFLMNL WA IFCMFCL STYTANLAAV MVGEKIYEEL SGIHDPKLHH PSQGFRFGTV RESSAEDYVR QSFPEMHEYM RRYNVPATPD GVE YLKNDP EKLDAFIMDK ALLDYEVSID ADCKLLTVGK PFAIEGYGIG LPPNSPLTAN ISELISQYKS HGFMDMLHDK WYRV VPC UniProtKB: Glutamate receptor ionotropic, NMDA 3A |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | 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: ![]() |
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 |
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Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 225900 |
Initial angle assignment | Type: RANDOM ASSIGNMENT |
Final angle assignment | Type: RANDOM ASSIGNMENT |