+Open data
-Basic information
Entry | Database: PDB / ID: 7pbd | ||||||||||||
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Title | a1b3 GABA-A receptor + GABA | ||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / pLGIC GABA Neurotransmission | ||||||||||||
Function / homology | Function and homology information GABA receptor complex / inhibitory extracellular ligand-gated monoatomic ion channel activity / benzodiazepine receptor activity / cellular response to histamine / GABA receptor activation / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly / synaptic transmission, GABAergic ...GABA receptor complex / inhibitory extracellular ligand-gated monoatomic ion channel activity / benzodiazepine receptor activity / cellular response to histamine / GABA receptor activation / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / nervous system process / neurotransmitter receptor activity / roof of mouth development / Signaling by ERBB4 / chloride channel complex / GABA-ergic synapse / transmembrane transporter complex / regulation of postsynaptic membrane potential / chloride transmembrane transport / dendrite membrane / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / regulation of membrane potential / cytoplasmic vesicle membrane / postsynapse / postsynaptic membrane / neuron projection / synapse / signal transduction / identical protein binding / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) Lama glama (llama) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å | ||||||||||||
Authors | Miller, P.S. / Kasaragod, V.B. | ||||||||||||
Funding support | United Kingdom, 1items
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Citation | Journal: Nature / Year: 2022 Title: Mechanisms of inhibition and activation of extrasynaptic αβ GABA receptors. Authors: Vikram Babu Kasaragod / Martin Mortensen / Steven W Hardwick / Ayla A Wahid / Valentina Dorovykh / Dimitri Y Chirgadze / Trevor G Smart / Paul S Miller / Abstract: Type A GABA (γ-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of α-, β-, γ-, δ-, ε-, ρ-, θ- and π-subunits. αβ, ...Type A GABA (γ-aminobutyric acid) receptors represent a diverse population in the mammalian brain, forming pentamers from combinations of α-, β-, γ-, δ-, ε-, ρ-, θ- and π-subunits. αβ, α4βδ, α6βδ and α5βγ receptors favour extrasynaptic localization, and mediate an essential persistent (tonic) inhibitory conductance in many regions of the mammalian brain. Mutations of these receptors in humans are linked to epilepsy and insomnia. Altered extrasynaptic receptor function is implicated in insomnia, stroke and Angelman and Fragile X syndromes, and drugs targeting these receptors are used to treat postpartum depression. Tonic GABAergic responses are moderated to avoid excessive suppression of neuronal communication, and can exhibit high sensitivity to Zn blockade, in contrast to synapse-preferring α1βγ, α2βγ and α3βγ receptor responses. Here, to resolve these distinctive features, we determined structures of the predominantly extrasynaptic αβ GABA receptor class. An inhibited state bound by both the lethal paralysing agent α-cobratoxin and Zn was used in comparisons with GABA-Zn and GABA-bound structures. Zn nullifies the GABA response by non-competitively plugging the extracellular end of the pore to block chloride conductance. In the absence of Zn, the GABA signalling response initially follows the canonical route until it reaches the pore. In contrast to synaptic GABA receptors, expansion of the midway pore activation gate is limited and it remains closed, reflecting the intrinsic low efficacy that characterizes the extrasynaptic receptor. Overall, this study explains distinct traits adopted by αβ receptors that adapt them to a role in tonic signalling. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7pbd.cif.gz | 360.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7pbd.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7pbd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7pbd_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 7pbd_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 7pbd_validation.xml.gz | 58.5 KB | Display | |
Data in CIF | 7pbd_validation.cif.gz | 86 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pb/7pbd ftp://data.pdbj.org/pub/pdb/validation_reports/pb/7pbd | HTTPS FTP |
-Related structure data
Related structure data | 13290MC 7pbzC 7pc0C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Gamma-aminobutyric acid receptor subunit alpha- ... , 2 types, 2 molecules AD
#1: Protein | Mass: 41991.133 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GABRA1 / Production host: Homo sapiens (human) / References: UniProt: P14867 |
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#3: Protein | Mass: 47059.648 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GABRA1 / Production host: Homo sapiens (human) / References: UniProt: P14867 |
-Protein / Antibody , 2 types, 4 molecules BCEF
#2: Protein | Mass: 51615.117 Da / Num. of mol.: 3 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GABRB3 / Production host: Homo sapiens (human) / References: UniProt: P28472 #4: Antibody | | Mass: 56329.621 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli) |
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-Sugars , 3 types, 8 molecules
#5: Polysaccharide | Source method: isolated from a genetically manipulated source #6: Polysaccharide | #8: Sugar | |
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-Non-polymers , 2 types, 3 molecules
#7: Chemical | #9: Chemical | ChemComp-HSM / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 0.22 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 7.4 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.25 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: UltrAuFoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 287 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: DIFFRACTION / Nominal magnification: 130000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm / C2 aperture diameter: 50 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 54.7 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 139537 / Symmetry type: POINT |