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Open data
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Basic information
| Entry | Database: PDB / ID: 9qk1 | |||||||||
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| Title | GABA-A receptor a2b3 (1:4) + a2NB06(silent) + b3Mb125 + GABA | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / pLGIC GABA Neurotransmission | |||||||||
| Function / homology | Function and homology informationbenzodiazepine 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 | |||||||||
| Biological species | Homo sapiens (human)![]() ![]() | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.05 Å | |||||||||
Authors | Miller, P.S. / Gonzalez-Prada, J.E. | |||||||||
| Funding support | United Kingdom, 1items
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Citation | Journal: Sci Adv / Year: 2026Title: 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 |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9qk1.cif.gz | 826.5 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9qk1.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9qk1.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qk/9qk1 ftp://data.pdbj.org/pub/pdb/validation_reports/qk/9qk1 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 53216MC ![]() 9qjpC ![]() 9qjqC ![]() 9qjrC ![]() 9qjsC ![]() 9qjvC ![]() 9qjxC ![]() 9qjyC ![]() 9qk0C ![]() 9tnbC ![]() 9tnsC ![]() 9tpqC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Gamma-aminobutyric acid receptor subunit ... , 2 types, 5 molecules ABCDE
| #1: Protein | Mass: 41495.488 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GABRA2 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: P47869 |
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| #2: Protein | Mass: 51615.117 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human), (gene. exp.) ![]() Gene: GABRB3, cybC / Production host: Homo sapiens (human) / References: UniProt: P28472, UniProt: P0ABE7 |
-Antibody , 2 types, 4 molecules FGHI
| #3: Antibody | Mass: 14408.728 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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| #4: Antibody | Mass: 14771.198 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Sugars , 3 types, 10 molecules 
| #5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Polysaccharide | alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #7: Sugar | |
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-Non-polymers , 2 types, 4 molecules 


| #8: Chemical | ChemComp-ABU / |
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| #9: Chemical |
-Details
| Has ligand of interest | Y |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: GABA-A receptor a2b3 (1:4) + a2NB06 + b3Mb125 + GABA / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.38 MDa / Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) / Cell: Expi293F |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
| Electron lens | Mode: DIFFRACTION / Nominal defocus max: 2500 nm / Nominal defocus min: 900 nm |
| Image recording | Electron dose: 51.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.05 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 142272 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Highest resolution: 3.05 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)


United Kingdom, 1items
Citation
























PDBj












FIELD EMISSION GUN