[English] 日本語
Yorodumi
- PDB-7teb: Cryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 non-active... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7teb
TitleCryo-EM structure of GluN1b-2B NMDAR complexed to Fab2 non-active1-like
Components
  • Fab2 heavy chain
  • Fab2 light chain
  • Glutamate receptor ionotropic, NMDA 1
  • Glutamate receptor ionotropic, NMDA 2B
KeywordsSIGNALING PROTEIN/IMMUNE SYSTEM / Channel / antibody / SIGNALING PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane ...pons maturation / positive regulation of Schwann cell migration / regulation of cell communication / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / olfactory learning / dendritic branch / conditioned taste aversion / regulation of respiratory gaseous exchange / protein localization to postsynaptic membrane / propylene metabolic process / response to glycine / regulation of monoatomic cation transmembrane transport / voltage-gated monoatomic cation channel activity / Synaptic adhesion-like molecules / NMDA glutamate receptor activity / RAF/MAP kinase cascade / parallel fiber to Purkinje cell synapse / NMDA selective glutamate receptor complex / response to morphine / calcium ion transmembrane import into cytosol / glutamate binding / neuromuscular process / protein heterotetramerization / regulation of synapse assembly / positive regulation of calcium ion transport into cytosol / positive regulation of reactive oxygen species biosynthetic process / glycine binding / male mating behavior / regulation of axonogenesis / regulation of dendrite morphogenesis / suckling behavior / startle response / response to amine / monoatomic cation transmembrane transport / regulation of neuronal synaptic plasticity / associative learning / monoatomic cation transport / social behavior / excitatory synapse / ligand-gated monoatomic ion channel activity / positive regulation of excitatory postsynaptic potential / cellular response to glycine / positive regulation of dendritic spine maintenance / Unblocking of NMDA receptors, glutamate binding and activation / cellular response to manganese ion / phosphatase binding / glutamate receptor binding / long-term memory / regulation of neuron apoptotic process / prepulse inhibition / monoatomic cation channel activity / calcium ion homeostasis / glutamate-gated receptor activity / synaptic cleft / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / sensory perception of pain / response to amphetamine / ionotropic glutamate receptor signaling pathway / hippocampal mossy fiber to CA3 synapse / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / adult locomotory behavior / excitatory postsynaptic potential / learning / synaptic transmission, glutamatergic / synaptic membrane / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / postsynaptic density membrane / regulation of long-term neuronal synaptic plasticity / visual learning / calcium channel activity / regulation of synaptic plasticity / terminal bouton / response to organic cyclic compound / cerebral cortex development / memory / synaptic vesicle membrane / response to calcium ion / intracellular calcium ion homeostasis / neuron cellular homeostasis / calcium ion transport / rhythmic process / synaptic vesicle / signaling receptor activity / presynaptic membrane / amyloid-beta binding / protein-containing complex assembly / chemical synaptic transmission / postsynaptic membrane / response to ethanol / negative regulation of neuron apoptotic process / transcription by RNA polymerase II / dendritic spine / postsynaptic density / learning or memory
Similarity search - Function
Gliding motility-associated protein, GldL / GldL N-terminal domain / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : ...Gliding motility-associated protein, GldL / GldL N-terminal domain / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I
Similarity search - Domain/homology
Glutamate receptor ionotropic, NMDA 1 / Gliding motility protein GldL
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.23 Å
AuthorsTajima, N. / Furukawa, H.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)MH085926 United States
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)NS111745 United States
CitationJournal: Nat Commun / Year: 2022
Title: Development and characterization of functional antibodies targeting NMDA receptors.
Authors: Nami Tajima / Noriko Simorowski / Remy A Yovanno / Michael C Regan / Kevin Michalski / Ricardo Gómez / Albert Y Lau / Hiro Furukawa /
Abstract: N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct ...N-methyl-D-aspartate receptors (NMDARs) are critically involved in basic brain functions and neurodegeneration as well as tumor invasiveness. Targeting specific subtypes of NMDARs with distinct activities has been considered an effective therapeutic strategy for neurological disorders and diseases. However, complete elimination of off-target effects of small chemical compounds has been challenging and thus, there is a need to explore alternative strategies for targeting NMDAR subtypes. Here we report identification of a functional antibody that specifically targets the GluN1-GluN2B NMDAR subtype and allosterically down-regulates ion channel activity as assessed by electrophysiology. Through biochemical analysis, x-ray crystallography, single-particle electron cryomicroscopy, and molecular dynamics simulations, we show that this inhibitory antibody recognizes the amino terminal domain of the GluN2B subunit and increases the population of the non-active conformational state. The current study demonstrates that antibodies may serve as specific reagents to regulate NMDAR functions for basic research and therapeutic objectives.
History
DepositionJan 4, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 2, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-25844
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2B
C: Glutamate receptor ionotropic, NMDA 1
D: Glutamate receptor ionotropic, NMDA 2B
H: Fab2 heavy chain
L: Fab2 light chain
M: Fab2 heavy chain
N: Fab2 light chain


Theoretical massNumber of molelcules
Total (without water)486,4598
Polymers486,4598
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Glutamate receptor ionotropic, NMDA 1 / GluN1 / Glutamate [NMDA] receptor subunit zeta-1 / N-methyl-D-aspartate receptor subunit NR1 / NMD-R1


Mass: 96944.891 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin1, Nmdar1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P35439
#2: Protein Glutamate receptor ionotropic, NMDA 2B / GluN2B / Glutamate [NMDA] receptor subunit epsilon-2 / N-methyl D-aspartate receptor subtype 2B / ...GluN2B / Glutamate [NMDA] receptor subunit epsilon-2 / N-methyl D-aspartate receptor subtype 2B / NMDAR2B / NR2B


Mass: 98797.820 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Grin2b / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q00960
#3: Protein Fab2 heavy chain


Mass: 23914.781 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
#4: Antibody Fab2 light chain


Mass: 23572.031 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: GluN1b-2B NMDAR - Fab2 / Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
Molecular weightExperimental value: NO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: OTHER / Nominal defocus max: 3500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 65 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 4.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 30424 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more