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Yorodumi- EMDB-17107: CryoEM structure of human rho1 GABAA receptor in complex with inh... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-17107 | |||||||||
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Title | CryoEM structure of human rho1 GABAA receptor in complex with inhibitor TPMPA | |||||||||
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Keywords | GABAA receptor / rho1 / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information GABA receptor activation / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / gamma-aminobutyric acid signaling pathway / neurotransmitter receptor activity / chloride channel complex / transmembrane transporter complex / GABA-ergic synapse / chloride transmembrane transport ...GABA receptor activation / GABA-A receptor activity / GABA-gated chloride ion channel activity / GABA-A receptor complex / gamma-aminobutyric acid signaling pathway / neurotransmitter receptor activity / chloride channel complex / transmembrane transporter complex / GABA-ergic synapse / chloride transmembrane transport / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / modulation of chemical synaptic transmission / presynaptic membrane / chemical synaptic transmission / postsynaptic membrane / neuron projection / protein domain specific binding / glutamatergic synapse / synapse / protein-containing complex binding / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||
Authors | Chen F / Victor T / John C / Rebecca JH / Erik L | |||||||||
Funding support | Sweden, 1 items
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Citation | Journal: Neuron / Year: 2023 Title: Structure and dynamics of differential ligand binding in the human ρ-type GABA receptor. Authors: John Cowgill / Chen Fan / Nandan Haloi / Victor Tobiasson / Yuxuan Zhuang / Rebecca J Howard / Erik Lindahl / Abstract: The neurotransmitter γ-aminobutyric acid (GABA) drives critical inhibitory processes in and beyond the nervous system, partly via ionotropic type-A receptors (GABARs). Pharmacological properties of ...The neurotransmitter γ-aminobutyric acid (GABA) drives critical inhibitory processes in and beyond the nervous system, partly via ionotropic type-A receptors (GABARs). Pharmacological properties of ρ-type GABARs are particularly distinctive, yet the structural basis for their specialization remains unclear. Here, we present cryo-EM structures of a lipid-embedded human ρ1 GABAR, including a partial intracellular domain, under apo, inhibited, and desensitized conditions. An apparent resting state, determined first in the absence of modulators, was recapitulated with the specific inhibitor (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid and blocker picrotoxin and provided a rationale for bicuculline insensitivity. Comparative structures, mutant recordings, and molecular simulations with and without GABA further explained the sensitized but slower activation of ρ1 relative to canonical subtypes. Combining GABA with picrotoxin also captured an apparent uncoupled intermediate state. This work reveals structural mechanisms of gating and modulation with applications to ρ-specific pharmaceutical design and to our biophysical understanding of ligand-gated ion channels. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_17107.map.gz | 23.1 MB | EMDB map data format | |
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Header (meta data) | emd-17107-v30.xml emd-17107.xml | 16.4 KB 16.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_17107_fsc.xml | 14.9 KB | Display | FSC data file |
Images | emd_17107.png | 195.4 KB | ||
Filedesc metadata | emd-17107.cif.gz | 5.9 KB | ||
Others | emd_17107_half_map_1.map.gz emd_17107_half_map_2.map.gz | 225.5 MB 225.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-17107 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-17107 | HTTPS FTP |
-Validation report
Summary document | emd_17107_validation.pdf.gz | 750.8 KB | Display | EMDB validaton report |
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Full document | emd_17107_full_validation.pdf.gz | 750.4 KB | Display | |
Data in XML | emd_17107_validation.xml.gz | 22.5 KB | Display | |
Data in CIF | emd_17107_validation.cif.gz | 29.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17107 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-17107 | HTTPS FTP |
-Related structure data
Related structure data | 8oq7MC 8op9C 8oq6C 8oq8C 8oqaC M: atomic model generated by this map C: citing same article (ref.) |
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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_17107.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.6725 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_17107_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_17107_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : human rho1 GABAA receptor
+Supramolecule #1: human rho1 GABAA receptor
+Macromolecule #1: Gamma-aminobutyric acid receptor subunit rho-1
+Macromolecule #2: methyl(1,2,3,6-tetrahydropyridin-4-yl)phosphinic acid
+Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #4: HEXANE
+Macromolecule #5: N-OCTANE
+Macromolecule #6: DODECANE
+Macromolecule #7: DECANE
+Macromolecule #8: CHLORIDE ION
+Macromolecule #9: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 46.12 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |