[English] 日本語
Yorodumi
- EMDB-53212: GABA-A receptor a2b3 (1:4) + a2NB47(silent) + b3Mb125 + GABA -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-53212
TitleGABA-A receptor a2b3 (1:4) + a2NB47(silent) + b3Mb125 + GABA
Map dataGABA-A-Ra2b3(1:4) a2VHH47 b3Mb125
Sample
  • Complex: GABA-A receptor a2b3 (1:4) + a2NB47 + b3Mb125 + GABA
    • Protein or peptide: Gamma-aminobutyric acid receptor subunit alpha-2
    • Protein or peptide: Gamma-aminobutyric acid receptor subunit beta-3,Soluble cytochrome b562
    • Protein or peptide: a2NB47
    • Protein or peptide: Mb125
  • Ligand: GAMMA-AMINO-BUTANOIC ACID
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: HISTAMINE
KeywordspLGIC GABA Neurotransmission / MEMBRANE PROTEIN
Function / homology
Function and homology information


benzodiazepine receptor activity / inhibitory synapse / extrasynaptic signaling via GABA / cellular response to histamine / inner ear receptor cell development / GABA receptor activation / negative regulation of synaptic transmission, GABAergic / innervation / GABA-gated chloride ion channel activity / GABA-A receptor complex ...benzodiazepine receptor activity / inhibitory synapse / extrasynaptic signaling via GABA / cellular response to histamine / inner ear receptor cell development / GABA receptor activation / negative regulation of synaptic transmission, GABAergic / innervation / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / GABA-A receptor activity / roof of mouth development / inhibitory postsynaptic potential / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / postsynaptic specialization membrane / Signaling by ERBB4 / cochlea development / chloride channel complex / cytoplasmic vesicle membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / dendrite membrane / chloride transmembrane transport / electron transport chain / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / GABA-ergic synapse / synaptic vesicle membrane / dendritic spine / electron transfer activity / periplasmic space / postsynaptic membrane / postsynapse / iron ion binding / axon / neuronal cell body / heme binding / cell surface / signal transduction / identical protein binding / plasma membrane
Similarity search - Function
Gamma-aminobutyric-acid A receptor, alpha 2 subunit / : / Gamma-aminobutyric-acid A receptor, alpha subunit / : / Gamma-aminobutyric-acid A receptor, beta subunit / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region ...Gamma-aminobutyric-acid A receptor, alpha 2 subunit / : / Gamma-aminobutyric-acid A receptor, alpha subunit / : / Gamma-aminobutyric-acid A receptor, beta subunit / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel / Neurotransmitter-gated ion-channel ligand-binding domain / Neurotransmitter-gated ion-channel ligand-binding domain superfamily / Neurotransmitter-gated ion-channel ligand binding domain
Similarity search - Domain/homology
Soluble cytochrome b562 / Gamma-aminobutyric acid receptor subunit beta-3 / Gamma-aminobutyric acid receptor subunit alpha-2
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.45 Å
AuthorsMiller PS / Gonzalez-Prada JE
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Biotechnology and Biological Sciences Research Council (BBSRC)BB/M024709/1 United Kingdom
CitationJournal: Sci Adv / Year: 2026
Title: Determining the molecular and physiological actions of subtype-selective nanobodies of GABA receptors.
Authors: Jose Enrique Gonzalez-Prada / Sulin Liu / Chuhan Shang / Chloe S Chernoff / Damian P Bright / Martin Mortensen / Charlotte F Jones / Stephanie Nestorow / Vikram Babu Kasaragod / Wan-Na Chen ...Authors: Jose Enrique Gonzalez-Prada / Sulin Liu / Chuhan Shang / Chloe S Chernoff / Damian P Bright / Martin Mortensen / Charlotte F Jones / Stephanie Nestorow / Vikram Babu Kasaragod / Wan-Na Chen / Saad Hannan / Jianchong Zhou / Alexander W E Dunn / Asma Soltani / Richard J Turner / Natasha M Duggan / Yin Yuan / Ayla A Wahid / Steven W Hardwick / Suzanne Scott / Dimitri Y Chirgadze / Els Pardon / Jan Steyaert / A Radu Aricescu / Ole Paulsen / David Belin / Trevor G Smart / Paul S Miller /
Abstract: γ-Aminobutyric acid type-A (GABA) receptors are the principal mediators of inhibitory neurotransmission in the human central nervous system. The α- and α-containing subtypes have tightly ...γ-Aminobutyric acid type-A (GABA) receptors are the principal mediators of inhibitory neurotransmission in the human central nervous system. The α- and α-containing subtypes have tightly controlled spatial expression profiles, which influence anxiety, nociception, epilepsy, and autism. α/α-Selective small molecules compromise on strength of effect (efficacy) to avoid off-subtype modulation. To break this pharmacological deadlock, we study here a panel of nanobodies (NBs) raised against α- and α-containing GABA receptors. We identify subtype selective silent binders, positive allosteric modulators (PAMs), and inhibitors. Cryo-electron microscopy structures explain the binding modes and molecular mechanisms of action of representative NBs. Modulators exhibit distinct synaptic and extrasynaptic functional profiles in brain slices and neuronal networks and can reduce anxiety in vivo. These selective and efficacious NBs (whether inhibitors or positive modulators) enable strong yet precise pharmacological control of α/α-containing subtypes to advance basic research and as potential therapeutic leads to treat neuropsychiatric disorders.
History
DepositionMar 19, 2025-
Header (metadata) releaseAug 26, 2026-
Map releaseAug 26, 2026-
UpdateAug 26, 2026-
Current statusAug 26, 2026Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_53212.png

Downloads & links

-
Map

FileDownload / File: emd_53212.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationGABA-A-Ra2b3(1:4) a2VHH47 b3Mb125
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.05 Å/pix.
x 320 pix.
= 336. Å		1.05 Å/pix.
x 320 pix.
= 336. Å		1.05 Å/pix.
x 320 pix.
= 336. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.05 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.158
Minimum - Maximum-0.26823798 - 0.7894255
Average (Standard dev.)-0.0003713136 (±0.02098875)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 336.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: GABA-A-Ra2b3(1:4) a2VHH47 b3Mb125

Fileemd_53212_half_map_1.map
AnnotationGABA-A-Ra2b3(1:4) a2VHH47 b3Mb125
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: GABA-A-Ra2b3(1:4) a2VHH47 b3Mb125

Fileemd_53212_half_map_2.map
AnnotationGABA-A-Ra2b3(1:4) a2VHH47 b3Mb125
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : GABA-A receptor a2b3 (1:4) + a2NB47 + b3Mb125 + GABA

EntireName: GABA-A receptor a2b3 (1:4) + a2NB47 + b3Mb125 + GABA
Components
  • Complex: GABA-A receptor a2b3 (1:4) + a2NB47 + b3Mb125 + GABA
    • Protein or peptide: Gamma-aminobutyric acid receptor subunit alpha-2
    • Protein or peptide: Gamma-aminobutyric acid receptor subunit beta-3,Soluble cytochrome b562
    • Protein or peptide: a2NB47
    • Protein or peptide: Mb125
  • Ligand: GAMMA-AMINO-BUTANOIC ACID
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: HISTAMINE

-
Supramolecule #1: GABA-A receptor a2b3 (1:4) + a2NB47 + b3Mb125 + GABA

SupramoleculeName: GABA-A receptor a2b3 (1:4) + a2NB47 + b3Mb125 + GABA / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 380 KDa

-
Macromolecule #1: Gamma-aminobutyric acid receptor subunit alpha-2

MacromoleculeName: Gamma-aminobutyric acid receptor subunit alpha-2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 41.495488 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: NIQEDEAKNN ITIFTRILDR LLDGYDNRLR PGLGDSITEV FTNIYVTSFG PVSDTDMEYT IDVFFRQKWK DERLKFKGPM NILRLNNLM ASKIWTPDTF FHNGKKSVAH NMTMPNKLLR IQDDGTLLYT MRLTVQAECP MHLEDFPMDA HSCPLKFGSY A YTTSEVTY ...String:
NIQEDEAKNN ITIFTRILDR LLDGYDNRLR PGLGDSITEV FTNIYVTSFG PVSDTDMEYT IDVFFRQKWK DERLKFKGPM NILRLNNLM ASKIWTPDTF FHNGKKSVAH NMTMPNKLLR IQDDGTLLYT MRLTVQAECP MHLEDFPMDA HSCPLKFGSY A YTTSEVTY IWTYNASDSV QVAPDGSRLN QYDLLGQSIG KETIKSSTGE YTVMTAHFHL KRKIGYFVIQ TYLPCIMTVI LS QVSFWLN RESVPARTVF GVTTVLTMTT LSISARNSLP KVAYATAMDW FIAVCYAFVF SALIEFATVN YFTKSQPARA AKI DRMSRI VFPVLFGTFN LVYWATYLNR EPVLGVSPGT TETSQVAPA

UniProtKB: Gamma-aminobutyric acid receptor subunit alpha-2, Gamma-aminobutyric acid receptor subunit alpha-2

-
Macromolecule #2: Gamma-aminobutyric acid receptor subunit beta-3,Soluble cytochrom...

MacromoleculeName: Gamma-aminobutyric acid receptor subunit beta-3,Soluble cytochrome b562
type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 51.615117 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: QSVNDPGNMS FVKETVDKLL KGYDIRLRPD FGGPPVCVGM NIDIASIDMV SEVNMDYTLT MYFQQYWRDK RLAYSGIPLN LTLDNRVAD QLWVPDTYFL NDKKSFVHGV TVKNRMIRLH PDGTVLYGLR ITTTAACMMD LRRYPLDEQN CTLEIESYGY T TDDIEFYW ...String:
QSVNDPGNMS FVKETVDKLL KGYDIRLRPD FGGPPVCVGM NIDIASIDMV SEVNMDYTLT MYFQQYWRDK RLAYSGIPLN LTLDNRVAD QLWVPDTYFL NDKKSFVHGV TVKNRMIRLH PDGTVLYGLR ITTTAACMMD LRRYPLDEQN CTLEIESYGY T TDDIEFYW RGGDKAVTGV ERIELPQFSI VEHRLVSRNV VFATGAYPRL SLSFRLKRNI GYFILQTYMP SILITILSWV SF WINYDAS AARVALGITT VLTMTTINTH LRETLPKIPY VKAIDMYLMG CFVFVFLALL EYAFVNYIFF SQPAGTADLE DNW ETLNDN LKVIEKADNA AQVKDALTKM RAAALDAQKA TPPKLEDKSP DSPEMKDFRH GFDILVGQID DALKLANEGK VKEA QAAAE QLKTTRNAYI QKYLTGRAAA IDRWSRIVFP FTFSLFNLVY WLYYVN

UniProtKB: Gamma-aminobutyric acid receptor subunit beta-3, Soluble cytochrome b562, Gamma-aminobutyric acid receptor subunit beta-3

-
Macromolecule #3: a2NB47

MacromoleculeName: a2NB47 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 15.184701 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLVESGGG LVQAGGSLRL SCAASGDTSS FYVTGWFRQA PGKEREFVGT ITSSSITYYA DAVEGRFTIS RDNAKNTVYL QMNSLKPED TAVYYCAARS PLDLVKTSDA LEAKWYRHWG QGTQVTVSSH HHHHHEPEA

-
Macromolecule #4: Mb125

MacromoleculeName: Mb125 / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 14.771198 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
QVQLVESGGG LVQGSLRLSC AASGHTFNYP IMGWFRQAPG KEREFVGAIS WSGGSTSYAD SVKDRFTISR DNAKNTVYLE MNNLKPEDT AVYYCAAKGR YSGGLYYPTN YDYWGQGTQV TVSSHHHHHH EPEA

-
Macromolecule #6: GAMMA-AMINO-BUTANOIC ACID

MacromoleculeName: GAMMA-AMINO-BUTANOIC ACID / type: ligand / ID: 6 / Number of copies: 1 / Formula: ABU
Molecular weightTheoretical: 103.12 Da
Chemical component information

ChemComp-ABU:
GAMMA-AMINO-BUTANOIC ACID / neurotransmitter, inhibitor*YM

-
Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 7 / Number of copies: 6 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

-
Macromolecule #8: HISTAMINE

MacromoleculeName: HISTAMINE / type: ligand / ID: 8 / Number of copies: 3 / Formula: HSM
Molecular weightTheoretical: 111.145 Da
Chemical component information

ChemComp-HSM:
HISTAMINE

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.4
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 51.5 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: SPOT SCAN / Imaging mode: DIFFRACTION / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.9 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 30394
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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