+Open data
-Basic information
Entry | Database: PDB / ID: 7pc0 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | GABA-A receptor bound by a-Cobratoxin | |||||||||
Components |
| |||||||||
Keywords | MEMBRANE PROTEIN / neurotransmission / toxin / GABA | |||||||||
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 / acetylcholine receptor inhibitor activity ...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 / acetylcholine receptor inhibitor activity / ion channel regulator activity / 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 / toxin activity / postsynapse / postsynaptic membrane / neuron projection / synapse / signal transduction / extracellular region / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Lama glama (llama) Homo sapiens (human) Naja kaouthia (monocled cobra) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3 Å | |||||||||
Authors | Kasaragod, V.B. / Miller, P.S. | |||||||||
Funding support | United Kingdom, 1items
| |||||||||
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 |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7pc0.cif.gz | 378 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7pc0.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 7pc0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7pc0_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7pc0_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7pc0_validation.xml.gz | 58.7 KB | Display | |
Data in CIF | 7pc0_validation.cif.gz | 81.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/pc/7pc0 ftp://data.pdbj.org/pub/pdb/validation_reports/pc/7pc0 | HTTPS FTP |
-Related structure data
Related structure data | 13315MC 7pbdC 7pbzC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Gamma-aminobutyric acid receptor subunit alpha- ... , 2 types, 2 molecules AD
#2: 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 |
---|---|
#4: 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 , 2 types, 5 molecules BCEKL
#3: 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 #5: Protein | Mass: 7842.094 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Naja kaouthia (monocled cobra) / References: UniProt: P01391 |
---|
-Antibody , 1 types, 1 molecules F
#1: 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) |
---|
-Sugars , 5 types, 8 molecules
#6: 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 |
---|---|
#7: 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 |
#8: Polysaccharide | alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D- ...alpha-D-mannopyranose-(1-3)-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 |
#9: 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 |
#10: Sugar | ChemComp-NAG / |
-Non-polymers , 3 types, 3 molecules
#11: Chemical | ChemComp-HSM / |
---|---|
#12: Chemical | ChemComp-ZN / |
#13: Chemical | ChemComp-HEX / |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
| ||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular weight | Value: 0.24 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
| ||||||||||||||||||||||||||||||
Source (recombinant) |
| ||||||||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
Specimen | Conc.: 0.25 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
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 defocus max: 1800 nm / Nominal defocus min: 600 nm |
Image recording | Average exposure time: 2.19 sec. / Electron dose: 50.69 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 78662 / Symmetry type: POINT |