[English] 日本語
Yorodumi
- PDB-7te6: Crystal structure of GluN1b-2B ATD complexed to Fab5 anti-GluN2B ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7te6
TitleCrystal structure of GluN1b-2B ATD complexed to Fab5 anti-GluN2B antibody
Components
  • Fab5 heavy chain
  • Fab5 light chain
  • Glutamate receptor ionotropic, NMDA 1
  • Glutamate receptor ionotropic, NMDA 2B
KeywordsSIGNALING PROTEIN/IMMUNE SYSTEM / Fab fragment complexed to the receptor / SIGNALING PROTEIN-IMMUNE SYSTEM complex
Function / homology
Function and homology information


cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / cellular response to curcumin / regulation of cAMP/PKA signal transduction / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / auditory behavior / sensitization / response to other organism ...cellular response to corticosterone stimulus / cellular response to magnesium starvation / sensory organ development / cellular response to curcumin / regulation of cAMP/PKA signal transduction / EPHB-mediated forward signaling / Assembly and cell surface presentation of NMDA receptors / auditory behavior / sensitization / response to other organism / response to hydrogen sulfide / dendritic branch / fear response / response to methylmercury / regulation of ARF protein signal transduction / apical dendrite / response to manganese ion / suckling behavior / interleukin-1 receptor binding / response to carbohydrate / cellular response to lipid / cellular response to dsRNA / RAF/MAP kinase cascade / negative regulation of dendritic spine maintenance / positive regulation of inhibitory postsynaptic potential / response to amine / response to growth hormone / heterocyclic compound binding / Synaptic adhesion-like molecules / response to glycoside / regulation of monoatomic cation transmembrane transport / NMDA glutamate receptor activity / NMDA selective glutamate receptor complex / glutamate binding / response to zinc ion / ligand-gated sodium channel activity / calcium ion transmembrane import into cytosol / positive regulation of glutamate secretion / protein heterotetramerization / small molecule binding / glycine binding / receptor clustering / startle response / parallel fiber to Purkinje cell synapse / regulation of MAPK cascade / regulation of postsynaptic membrane potential / behavioral response to pain / extracellularly glutamate-gated ion channel activity / monoatomic cation transmembrane transport / associative learning / response to electrical stimulus / action potential / response to magnesium ion / Unblocking of NMDA receptors, glutamate binding and activation / regulation of neuronal synaptic plasticity / monoatomic cation transport / glutamate receptor binding / detection of mechanical stimulus involved in sensory perception of pain / ligand-gated monoatomic ion channel activity / multicellular organismal response to stress / response to mechanical stimulus / neuron development / long-term memory / postsynaptic density, intracellular component / behavioral fear response / monoatomic cation channel activity / synaptic cleft / response to fungicide / 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 / response to cytokine / D2 dopamine receptor binding / cell adhesion molecule binding / ionotropic glutamate receptor signaling pathway / ionotropic glutamate receptor binding / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / protein tyrosine kinase binding / cellular response to forskolin / positive regulation of excitatory postsynaptic potential / hippocampal mossy fiber to CA3 synapse / protein serine/threonine kinase binding / sodium ion transmembrane transport / learning / response to nicotine / synaptic membrane / response to amphetamine / hippocampus development / response to cocaine / cellular response to amino acid stimulus / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of membrane potential / excitatory postsynaptic potential / cerebral cortex development / response to calcium ion / regulation of synaptic plasticity
Similarity search - Function
Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / : ...Glutamate [NMDA] receptor, epsilon subunit, C-terminal / N-methyl D-aspartate receptor 2B3 C-terminus / : / : / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / : / 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 / Glutamate receptor ionotropic, NMDA 2B
Similarity search - Component
Biological speciesXenopus laevis (African clawed frog)
Rattus norvegicus (Norway rat)
Mus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 4.55 Å
AuthorsRegan, M. / Tajima, 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 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2B
C: Fab5 heavy chain
D: Fab5 light chain
E: Glutamate receptor ionotropic, NMDA 1
F: Glutamate receptor ionotropic, NMDA 2B
G: Fab5 heavy chain
H: Fab5 light chain


Theoretical massNumber of molelcules
Total (without water)264,0008
Polymers264,0008
Non-polymers00
Water00
1
A: Glutamate receptor ionotropic, NMDA 1
B: Glutamate receptor ionotropic, NMDA 2B
C: Fab5 heavy chain
D: Fab5 light chain


Theoretical massNumber of molelcules
Total (without water)132,0004
Polymers132,0004
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
E: Glutamate receptor ionotropic, NMDA 1
F: Glutamate receptor ionotropic, NMDA 2B
G: Fab5 heavy chain
H: Fab5 light chain


Theoretical massNumber of molelcules
Total (without water)132,0004
Polymers132,0004
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)124.922, 124.922, 407.119
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212

-
Components

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


Mass: 42932.055 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: grin1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A1L8F5J9
#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: 41367.902 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: Antibody Fab5 heavy chain


Mass: 23844.684 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)
#4: Antibody Fab5 light chain


Mass: 23855.256 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Mus musculus (house mouse)

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.01 Å3/Da / Density % sol: 59.11 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop
Details: 2.1 M sodium/potassium phosphate, 100 mM lithium sulfate, 100 mM CAPS, pH 10.5, 4% formamide

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Oct 10, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1 Å / Relative weight: 1
ReflectionResolution: 4.54→30 Å / Num. obs: 17965 / % possible obs: 97.5 % / Redundancy: 7.7 % / Rmerge(I) obs: 0.156 / Net I/σ(I): 6.2
Reflection shellResolution: 4.54→4.66 Å / Num. unique obs: 1644 / CC1/2: 0.534

-
Processing

Software
NameVersionClassification
HKL-2000data reduction
PHENIX1.13_2998refinement
PDB_EXTRACT3.27data extraction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entries 5B3J & 3QEL

5b3j

3qel


Resolution: 4.55→24.984 Å / SU ML: 0.77 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 33.7 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3242 916 5.1 %
Rwork0.2816 17049 -
obs0.2838 17965 93.27 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 222.11 Å2 / Biso mean: 83.7583 Å2 / Biso min: 38.55 Å2
Refinement stepCycle: final / Resolution: 4.55→24.984 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms17193 0 0 0 17193
Num. residues----2206
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
4.5505-4.78880.42681070.33181772
4.7888-5.08650.37131180.3196216285
5.0865-5.47540.39311280.304246596
5.4754-6.01940.36071350.31432578100
6.0194-6.87450.32711370.30862595100
6.8745-8.6020.25191420.25332648100
8.602-24.9840.25841490.2269278499

+
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