+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13315 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | GABA-A receptor bound by a-Cobratoxin | |||||||||
Map data | Main map | |||||||||
Sample |
| |||||||||
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 | Homo sapiens (human) / Naja kaouthia (monocled cobra) / Lama glama (llama) / monocled cobra (monocled cobra) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Kasaragod VB / Hardwick SW / Chirgadze DY / Miller PS | |||||||||
Funding support | United Kingdom, 1 items
| |||||||||
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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_13315.map.gz | 122.2 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-13315-v30.xml emd-13315.xml | 22.2 KB 22.2 KB | Display Display | EMDB header |
Images | emd_13315.png | 132.9 KB | ||
Others | emd_13315_half_map_1.map.gz emd_13315_half_map_2.map.gz | 226.5 MB 226.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13315 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13315 | HTTPS FTP |
-Validation report
Summary document | emd_13315_validation.pdf.gz | 492.2 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_13315_full_validation.pdf.gz | 491.8 KB | Display | |
Data in XML | emd_13315_validation.xml.gz | 15.8 KB | Display | |
Data in CIF | emd_13315_validation.cif.gz | 18.6 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13315 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13315 | HTTPS FTP |
-Related structure data
Related structure data | 7pc0MC 7pbdC 7pbzC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_13315.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Main map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Half map: Halfmap A
File | emd_13315_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Halfmap_A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Halfmap B
File | emd_13315_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Halfmap_B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : GABA-A receptor pentamer bound by Cobratoxin
+Supramolecule #1: GABA-A receptor pentamer bound by Cobratoxin
+Supramolecule #3: GABA-A receptor pentamer
+Supramolecule #4: Cobratoxin
+Supramolecule #2: Megabody 25
+Macromolecule #1: Megabody 25
+Macromolecule #2: Gamma-aminobutyric acid receptor subunit alpha-1
+Macromolecule #3: Gamma-aminobutyric acid receptor subunit beta-3
+Macromolecule #4: Gamma-aminobutyric acid receptor subunit alpha-1
+Macromolecule #5: Alpha-cobratoxin
+Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #11: HISTAMINE
+Macromolecule #12: ZINC ION
+Macromolecule #13: HEXANE
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.25 mg/mL |
---|---|
Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 2.19 sec. / Average electron dose: 50.69 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: DIFFRACTION / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 78662 |
---|---|
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |