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- EMDB-17108: CryoEM structure of human rho1 GABAA receptor in complex with por... -
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Open data
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Basic information
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Title | CryoEM structure of human rho1 GABAA receptor in complex with pore blocker picrotoxin | |||||||||
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![]() | GABAA receptor / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() 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 | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||
![]() | Chen F / Victor T / John C / Rebecca JH / Erik L | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 25.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.8 KB 15.8 KB | Display Display | ![]() |
Images | ![]() | 189.1 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 225.1 MB 225.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8oq8MC ![]() 8op9C ![]() 8oq6C ![]() 8oq7C ![]() 8oqaC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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_17108_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_17108_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : rho1 GABAA receptor
Entire | Name: rho1 GABAA receptor |
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Components |
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-Supramolecule #1: rho1 GABAA receptor
Supramolecule | Name: rho1 GABAA receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Gamma-aminobutyric acid receptor subunit rho-1
Macromolecule | Name: Gamma-aminobutyric acid receptor subunit rho-1 / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 55.95023 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MLAVPNMRFG IFLLWWGWVL ATESRMHWPG REVHEMSKKG RPQRQRREVH EDAHKQVSPI LRRSPDITKS PLTKSEQLLR IDDHDFSMR PGFGGPAIPV GVDVQVESLD SISEVDMDFT MTLYLRHYWK DERLSFPSTN NLSMTFDGRL VKKIWVPDMF F VHSKRSFI ...String: MLAVPNMRFG IFLLWWGWVL ATESRMHWPG REVHEMSKKG RPQRQRREVH EDAHKQVSPI LRRSPDITKS PLTKSEQLLR IDDHDFSMR PGFGGPAIPV GVDVQVESLD SISEVDMDFT MTLYLRHYWK DERLSFPSTN NLSMTFDGRL VKKIWVPDMF F VHSKRSFI HDTTTDNVML RVQPDGKVLY SLRVTVTAMC NMDFSRFPLD TQTCSLEIES YAYTEDDLML YWKKGNDSLK TD ERISLSQ FLIQEFHTTT KLAFYSSTGW YNRLYINFTL RRHIFFFLLQ TYFPATLMVM LSWVSFWIDR RAVPARVPLG ITT VLTMST IITGVNASMP RVSYIKAVDI YLWVSFVFVF LSVLEYAAVN YLTTVQERKE QKLREKLPCT SGLPPPRTAM LDGN YSDGE VNDLDNYMPE NGEKPDRMMV QLTLASERSS PQRKSQRSSY VSMRIDTHAI DKYSRIIFPA AYILFNLIYW SIFS UniProtKB: Gamma-aminobutyric acid receptor subunit rho-1 |
-Macromolecule #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 10 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Macromolecule #3: HEXANE
Macromolecule | Name: HEXANE / type: ligand / ID: 3 / Number of copies: 15 / Formula: HEX |
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Molecular weight | Theoretical: 86.175 Da |
Chemical component information | ![]() ChemComp-HEX: |
-Macromolecule #4: DODECANE
Macromolecule | Name: DODECANE / type: ligand / ID: 4 / Number of copies: 10 / Formula: D12 |
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Molecular weight | Theoretical: 170.335 Da |
Chemical component information | ![]() ChemComp-D12: |
-Macromolecule #5: DECANE
Macromolecule | Name: DECANE / type: ligand / ID: 5 / Number of copies: 10 / Formula: D10 |
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Molecular weight | Theoretical: 142.282 Da |
Chemical component information | ![]() ChemComp-D10: |
-Macromolecule #6: (1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-2a-hydroxy-8b-methyl-9-(prop-1-en-...
Macromolecule | Name: (1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-2a-hydroxy-8b-methyl-9-(prop-1-en-2-yl)hexahydro-3,6-methano-1,5,7-trioxacyclopenta[ij]c yclopropa[a]azulene-4,8(3H)-dione type: ligand / ID: 6 / Number of copies: 1 / Formula: RI5 |
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Molecular weight | Theoretical: 292.284 Da |
-Macromolecule #7: water
Macromolecule | Name: water / type: ligand / ID: 7 / Number of copies: 132 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV |
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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: 41.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
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 |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 214978 |
Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |