[English] 日本語
Yorodumi
- EMDB-17110: CryoEM structure of human rho1 GABAA receptor in complex with GAB... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-17110
TitleCryoEM structure of human rho1 GABAA receptor in complex with GABA and picrotoxin
Map data
Sample
  • Complex: human rho1 GABAA receptor
    • Protein or peptide: Gamma-aminobutyric acid receptor subunit rho-1
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: HEXANE
  • Ligand: N-OCTANEOctane
  • Ligand: CHLORIDE IONChloride
  • Ligand: GAMMA-AMINO-BUTANOIC ACID
  • Ligand: (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
KeywordsGABAA receptor / rho1 / MEMBRANE PROTEIN
Function / homology
Function and homology information


GABA receptor activation / GABA-A receptor activity / GABA-A receptor complex / neurotransmitter receptor activity / gamma-aminobutyric acid signaling pathway / chloride channel activity / extracellular ligand-gated monoatomic ion channel activity / chloride channel complex / GABA-ergic synapse / chloride transmembrane transport ...GABA receptor activation / GABA-A receptor activity / GABA-A receptor complex / neurotransmitter receptor activity / gamma-aminobutyric acid signaling pathway / chloride channel activity / extracellular ligand-gated monoatomic ion channel activity / chloride channel 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 / synapse / glutamatergic synapse / protein-containing complex binding / identical protein binding / plasma membrane
Similarity search - Function
Gamma-aminobutyric-acid A receptor, Rho / Gamma-aminobutyric-acid A receptor, Rho1 / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel ...Gamma-aminobutyric-acid A receptor, Rho / Gamma-aminobutyric-acid A receptor, Rho1 / Gamma-aminobutyric acid A receptor/Glycine receptor alpha / Neurotransmitter-gated ion-channel, conserved site / Neurotransmitter-gated ion-channels signature. / Neurotransmitter-gated ion-channel transmembrane domain / Neurotransmitter-gated ion-channel transmembrane region / Neurotransmitter-gated ion-channel transmembrane domain superfamily / Neuronal acetylcholine receptor / Neurotransmitter-gated ion-channel / Neurotransmitter-gated ion-channel ligand-binding domain / Neurotransmitter-gated ion-channel ligand-binding domain superfamily / Neurotransmitter-gated ion-channel ligand binding domain
Similarity search - Domain/homology
Gamma-aminobutyric acid receptor subunit rho-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.9 Å
AuthorsChen F / Victor T / John C / Rebecca JH / Erik L
Funding support Sweden, 1 items
OrganizationGrant numberCountry
Swedish Research Council2019-02433 Sweden
CitationJournal: 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
DepositionApr 11, 2023-
Header (metadata) releaseAug 30, 2023-
Map releaseAug 30, 2023-
UpdateFeb 7, 2024-
Current statusFeb 7, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_17110.png

Downloads & links

-
Map

FileDownload / File: emd_17110.map.gz / Format: CCP4 / Size: 282.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.66 Å/pix.
x 420 pix.
= 279.09 Å		0.66 Å/pix.
x 420 pix.
= 279.09 Å		0.66 Å/pix.
x 420 pix.
= 279.09 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.6645 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.005
Minimum - Maximum-0.021299018 - 0.03220907
Average (Standard dev.)0.00000617503 (±0.0007526402)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions420420420
Spacing420420420
CellA=B=C: 279.09 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_17110_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_17110_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human rho1 GABAA receptor

EntireName: human rho1 GABAA receptor
Components
  • Complex: human rho1 GABAA receptor
    • Protein or peptide: Gamma-aminobutyric acid receptor subunit rho-1
  • Ligand: 2-acetamido-2-deoxy-beta-D-glucopyranose
  • Ligand: HEXANE
  • Ligand: N-OCTANEOctane
  • Ligand: CHLORIDE IONChloride
  • Ligand: GAMMA-AMINO-BUTANOIC ACID
  • Ligand: (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

-
Supramolecule #1: human rho1 GABAA receptor

SupramoleculeName: human rho1 GABAA receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Gamma-aminobutyric acid receptor subunit rho-1

MacromoleculeName: Gamma-aminobutyric acid receptor subunit rho-1 / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 55.95023 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

MacromoleculeName: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 2 / Number of copies: 10 / Formula: NAG
Molecular weightTheoretical: 221.208 Da
Chemical component information

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

-
Macromolecule #3: HEXANE

MacromoleculeName: HEXANE / type: ligand / ID: 3 / Number of copies: 14 / Formula: HEX
Molecular weightTheoretical: 86.175 Da
Chemical component information

ChemComp-HEX:
HEXANE / Hexane

-
Macromolecule #4: N-OCTANE

MacromoleculeName: N-OCTANE / type: ligand / ID: 4 / Number of copies: 4 / Formula: OCT
Molecular weightTheoretical: 114.229 Da
Chemical component information

ChemComp-OCT:
N-OCTANE / Octane

-
Macromolecule #5: CHLORIDE ION

MacromoleculeName: CHLORIDE ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: CL
Molecular weightTheoretical: 35.453 Da

-
Macromolecule #6: GAMMA-AMINO-BUTANOIC ACID

MacromoleculeName: GAMMA-AMINO-BUTANOIC ACID / type: ligand / ID: 6 / Number of copies: 5 / Formula: ABU
Molecular weightTheoretical: 103.12 Da
Chemical component information

ChemComp-ABU:
GAMMA-AMINO-BUTANOIC ACID / neurotransmitter, inhibitor*YM / Γ-Aminobutyric acid

-
Macromolecule #7: (1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-2a-hydroxy-8b-methyl-9-(prop-1-en-...

MacromoleculeName: (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: 7 / Number of copies: 1 / Formula: RI5
Molecular weightTheoretical: 292.284 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.2 µm
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 46.12 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Startup modelType of model: INSILICO MODEL
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 90439
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more