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Open data
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Basic information
| Entry | Database: PDB / ID: 9tns | |||||||||
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| Title | GABA-A receptor a3b3g2 + GABA-PRE + a3NB83 | |||||||||
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Keywords | MEMBRANE PROTEIN / pLGIC / GABA / Neurotransmission | |||||||||
| Function / homology | Function and homology informationbenzodiazepine receptor activity / extrasynaptic signaling via GABA / cellular response to histamine / GABA receptor activation / negative regulation of synaptic transmission, GABAergic / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / GABA-A receptor activity / synaptic transmission, GABAergic ...benzodiazepine receptor activity / extrasynaptic signaling via GABA / cellular response to histamine / GABA receptor activation / negative regulation of synaptic transmission, GABAergic / GABA-gated chloride ion channel activity / GABA-A receptor complex / inhibitory synapse assembly / GABA-A receptor activity / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / postsynaptic specialization membrane / chloride channel activity / Signaling by ERBB4 / chloride channel complex / cytoplasmic vesicle membrane / dendrite membrane / chloride transmembrane transport / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / GABA-ergic synapse / dendritic spine / postsynaptic membrane / postsynapse / axon / plasma membrane Similarity search - Function | |||||||||
| Biological species | Homo sapiens (human)![]() | |||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||
Authors | Shang, C. / Nestorow, S.A. / Miller, P.S. | |||||||||
| 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. | |||||||||
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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 | 9tns.cif.gz | 706.4 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9tns.ent.gz | Display | PDB format | |
| PDBx/mmJSON format | 9tns.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tn/9tns ftp://data.pdbj.org/pub/pdb/validation_reports/tn/9tns | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 56094MC ![]() 9qjpC ![]() 9qjqC ![]() 9qjrC ![]() 9qjsC ![]() 9qjvC ![]() 9qjxC ![]() 9qjyC ![]() 9qk0C ![]() 9qk1C ![]() 9tnbC ![]() 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, 3 molecules ADC
| #1: Protein | Mass: 43382.766 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Glvi linker sequence (SQPARAA). Region substituted: Arg337-Ser425,Glvi linker sequence (SQPARAA). Region substituted: Arg337-Ser425 Source: (gene. exp.) Homo sapiens (human) / Gene: GABRA3 / Production host: Homo sapiens (human) / References: UniProt: P34903#3: Protein | | Mass: 42798.875 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Includes an 1D4 tag at C-terminus of the sequence (TETSQVAPA), this is not resolved in density and not modelled. Glvi linker sequence (SQPARAA), region substituted Ser322-Ala408,Includes an ...Details: Includes an 1D4 tag at C-terminus of the sequence (TETSQVAPA), this is not resolved in density and not modelled. Glvi linker sequence (SQPARAA), region substituted Ser322-Ala408,Includes an 1D4 tag at C-terminus of the sequence (TETSQVAPA), this is not resolved in density and not modelled. Glvi linker sequence (SQPARAA), region substituted Ser322-Ala408 Source: (gene. exp.) Homo sapiens (human) / Gene: GABRG2 / Production host: Homo sapiens (human) / References: UniProt: P18507 |
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-Protein / Antibody / Non-polymers , 3 types, 5 molecules BEF

| #10: Chemical | | #2: Protein | Mass: 51615.117 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Details: Modified glvi sequence containing the Escherichia coli soluble cytochrome B562RIL41 (BRIL, amino acids 23-130, ADLE...QKYL, Uniprot P0ABE7) to give the sequence SQPAGT-BRIL-TGRAA. Linker ...Details: Modified glvi sequence containing the Escherichia coli soluble cytochrome B562RIL41 (BRIL, amino acids 23-130, ADLE...QKYL, Uniprot P0ABE7) to give the sequence SQPAGT-BRIL-TGRAA. Linker regions substituted Gly308-Asn421. This BRIL domain was present in the protein but not resolved in the cryo-EM density and is therefore not included in the atomic model. Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human)#4: Antibody | | Mass: 14582.058 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) |
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-Sugars , 5 types, 11 molecules 
| #5: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]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 | ||||||
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| #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Polysaccharide | Source method: isolated from a genetically manipulated source #8: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[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 #9: Sugar | ChemComp-NAG / |
-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
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| Buffer solution | pH: 7.6 Details: 75 millimolar sodium chloride; 12.5 millimolar HEPES, pH 7.6; 1.5 millimolar 1D4 peptide | ||||||||||||||||||||||||||||
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Nanodisc-reconstituted alpha3beta3gamma2 GABA-A receptor in complex with with GABA and nanobody a3NB83 | ||||||||||||||||||||||||||||
| Specimen support | Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||||||||||||||||||
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 277 K |
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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: OTHER | ||||||||||||||||||||||||
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 2200 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm | ||||||||||||||||||||||||
| Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER | ||||||||||||||||||||||||
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About Yorodumi




Homo sapiens (human)

United Kingdom, 1items
Citation
























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FIELD EMISSION GUN