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Yorodumi- PDB-6x3w: Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with ... -
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-Basic information
Entry | Database: PDB / ID: 6x3w | ||||||||||||||||||
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Title | Human GABAA receptor alpha1-beta2-gamma2 subtype in complex with GABA plus phenobarbital | ||||||||||||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Ion channel / Cys-loop receptor / pentametic ligand gated channel / GABAA receptor | ||||||||||||||||||
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 / GABA-ergic synapse / transmembrane transporter complex / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||
Authors | Kim, J.J. / Gharpure, A. / Teng, J. / Zhuang, Y. / Howard, R.J. / Zhu, S. / Noviello, C.M. / Walsh, R.M. / Lindahl, E. / Hibbs, R.E. | ||||||||||||||||||
Funding support | United States, 5items
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Citation | Journal: Nature / Year: 2020 Title: Shared structural mechanisms of general anaesthetics and benzodiazepines. Authors: Jeong Joo Kim / Anant Gharpure / Jinfeng Teng / Yuxuan Zhuang / Rebecca J Howard / Shaotong Zhu / Colleen M Noviello / Richard M Walsh / Erik Lindahl / Ryan E Hibbs / Abstract: Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA) receptors to dampen neuronal activity in the brain. However, direct ...Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABA) receptors to dampen neuronal activity in the brain. However, direct structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. Here we present cryo-electron microscopy structures of GABA receptors bound to intravenous anaesthetics, benzodiazepines and inhibitory modulators. These structures were solved in a lipidic environment and are complemented by electrophysiology and molecular dynamics simulations. Structures of GABA receptors in complex with the anaesthetics phenobarbital, etomidate and propofol reveal both distinct and common transmembrane binding sites, which are shared in part by the benzodiazepine drug diazepam. Structures in which GABA receptors are bound by benzodiazepine-site ligands identify an additional membrane binding site for diazepam and suggest an allosteric mechanism for anaesthetic reversal by flumazenil. This study provides a foundation for understanding how pharmacologically diverse and clinically essential drugs act through overlapping and distinct mechanisms to potentiate inhibitory signalling in the brain. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6x3w.cif.gz | 406.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6x3w.ent.gz | 321.9 KB | Display | PDB format |
PDBx/mmJSON format | 6x3w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6x3w_validation.pdf.gz | 1.7 MB | Display | wwPDB validaton report |
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Full document | 6x3w_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 6x3w_validation.xml.gz | 66 KB | Display | |
Data in CIF | 6x3w_validation.cif.gz | 99 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x3/6x3w ftp://data.pdbj.org/pub/pdb/validation_reports/x3/6x3w | HTTPS FTP |
-Related structure data
Related structure data | 22035MC 6x3sC 6x3tC 6x3uC 6x3vC 6x3xC 6x3zC 6x40C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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-Components
-Gamma-aminobutyric acid receptor subunit ... , 3 types, 5 molecules ACBDE
#1: Protein | Mass: 41810.086 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GABRB2 / Plasmid: pEZT-BM / Cell line (production host): HEK293S / Production host: Homo sapiens (human) / Variant (production host): GnTI- / References: UniProt: P47870 #2: Protein | Mass: 41061.211 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GABRA1 / Plasmid: pEZT-BM / Cell line (production host): HEK293S / Production host: Homo sapiens (human) / Variant (production host): GnTI- / References: UniProt: P14867 #3: Protein | | Mass: 47673.109 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) |
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