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Yorodumi- EMDB-40506: Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-40506 | |||||||||
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Title | Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus dehydroepiandrosterone sulfate | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Ion channel / neurosteroids / TRANSPORT PROTEIN | |||||||||
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 / inner ear receptor cell development / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly ...GABA receptor complex / inhibitory extracellular ligand-gated monoatomic ion channel activity / benzodiazepine receptor activity / cellular response to histamine / GABA receptor activation / inner ear receptor cell development / GABA-gated chloride ion channel activity / GABA-A receptor activity / GABA-A receptor complex / inhibitory synapse assembly / innervation / synaptic transmission, GABAergic / postsynaptic specialization membrane / gamma-aminobutyric acid signaling pathway / neurotransmitter receptor activity / adult behavior / cochlea development / chloride channel activity / Signaling by ERBB4 / chloride channel complex / transmembrane transporter complex / GABA-ergic synapse / regulation of postsynaptic membrane potential / chloride transmembrane transport / dendrite membrane / post-embryonic development / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / cytoplasmic vesicle membrane / postsynapse / chemical synaptic transmission / postsynaptic membrane / neuron projection / axon / synapse / extracellular exosome / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.71 Å | |||||||||
Authors | Legesse DH / Hibbs RE | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Commun / Year: 2023 Title: Structural insights into opposing actions of neurosteroids on GABA receptors. Authors: Dagimhiwat H Legesse / Chen Fan / Jinfeng Teng / Yuxuan Zhuang / Rebecca J Howard / Colleen M Noviello / Erik Lindahl / Ryan E Hibbs / Abstract: γ-Aminobutyric acid type A (GABA) receptors mediate fast inhibitory signaling in the brain and are targets of numerous drugs and endogenous neurosteroids. A subset of neurosteroids are GABA receptor ...γ-Aminobutyric acid type A (GABA) receptors mediate fast inhibitory signaling in the brain and are targets of numerous drugs and endogenous neurosteroids. A subset of neurosteroids are GABA receptor positive allosteric modulators; one of these, allopregnanolone, is the only drug approved specifically for treating postpartum depression. There is a consensus emerging from structural, physiological and photolabeling studies as to where positive modulators bind, but how they potentiate GABA activation remains unclear. Other neurosteroids are negative modulators of GABA receptors, but their binding sites remain debated. Here we present structures of a synaptic GABA receptor bound to allopregnanolone and two inhibitory sulfated neurosteroids. Allopregnanolone binds at the receptor-bilayer interface, in the consensus potentiator site. In contrast, inhibitory neurosteroids bind in the pore. MD simulations and electrophysiology support a mechanism by which allopregnanolone potentiates channel activity and suggest the dominant mechanism for sulfated neurosteroid inhibition is through pore block. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_40506.map.gz | 8.1 MB | EMDB map data format | |
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Header (meta data) | emd-40506-v30.xml emd-40506.xml | 21.8 KB 21.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_40506_fsc.xml | 10.2 KB | Display | FSC data file |
Images | emd_40506.png | 91 KB | ||
Filedesc metadata | emd-40506.cif.gz | 7.3 KB | ||
Others | emd_40506_half_map_1.map.gz emd_40506_half_map_2.map.gz | 71.2 MB 71.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-40506 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40506 | HTTPS FTP |
-Validation report
Summary document | emd_40506_validation.pdf.gz | 766.3 KB | Display | EMDB validaton report |
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Full document | emd_40506_full_validation.pdf.gz | 765.9 KB | Display | |
Data in XML | emd_40506_validation.xml.gz | 17.7 KB | Display | |
Data in CIF | emd_40506_validation.cif.gz | 22.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40506 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40506 | HTTPS FTP |
-Related structure data
Related structure data | 8sidMC 8sgoC 8si9C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_40506.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.0694 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_40506_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_40506_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with...
+Supramolecule #1: Human GABA-A receptor alpha1-beta2-gamma2 subtype in complex with...
+Macromolecule #1: Gamma-aminobutyric acid receptor subunit beta-2
+Macromolecule #2: Gamma-aminobutyric acid receptor subunit alpha-1
+Macromolecule #3: Gamma-aminobutyric acid receptor subunit gamma-2
+Macromolecule #4: Kappa Fab Light Chain
+Macromolecule #5: IgG2b Fab Heavy Chain
+Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #10: GAMMA-AMINO-BUTANOIC ACID
+Macromolecule #11: 17-oxoandrost-5-en-3beta-yl hydrogen sulfate
+Macromolecule #12: PHOSPHATIDYLETHANOLAMINE
+Macromolecule #13: O-[(R)-[(2S)-2-(hexadecanoyloxy)-3-(octadecanoyloxy)propoxy](hydr...
+Macromolecule #14: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 20.0 µm / Nominal defocus min: 8.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |