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Open data
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Basic information
Entry | Database: PDB / ID: 6w2x | |||||||||
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Title | CryoEM Structure of Inactive GABAB Heterodimer | |||||||||
![]() | (Gamma-aminobutyric acid type B receptor subunit ...) x 2 | |||||||||
![]() | SIGNALING PROTEIN / Inhibitor / Heterodimer / GPCR | |||||||||
Function / homology | ![]() G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / GABA B receptor activation / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / G protein-coupled GABA receptor complex / negative regulation of gamma-aminobutyric acid secretion / neuron-glial cell signaling / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / negative regulation of epinephrine secretion / negative regulation of dopamine secretion ...G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / GABA B receptor activation / G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential / G protein-coupled GABA receptor complex / negative regulation of gamma-aminobutyric acid secretion / neuron-glial cell signaling / G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / negative regulation of epinephrine secretion / negative regulation of dopamine secretion / positive regulation of growth hormone secretion / extracellular matrix protein binding / GABA receptor complex / negative regulation of adenylate cyclase activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / synaptic transmission, GABAergic / gamma-aminobutyric acid signaling pathway / positive regulation of glutamate secretion / negative regulation of synaptic transmission / axolemma / GABA-ergic synapse / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / dendritic shaft / response to nicotine / Schaffer collateral - CA1 synapse / mitochondrial membrane / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / transmembrane signaling receptor activity / osteoblast differentiation / synaptic vesicle / presynaptic membrane / G alpha (i) signalling events / chemical synaptic transmission / postsynaptic membrane / response to ethanol / dendritic spine / neuron projection / protein heterodimerization activity / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / neuronal cell body / glutamatergic synapse / endoplasmic reticulum membrane / extracellular space / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | |||||||||
![]() | Papasergi-Scott, M.M. / Robertson, M.J. / Skiniotis, G. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of metabotropic GABA receptor. Authors: Makaía M Papasergi-Scott / Michael J Robertson / Alpay B Seven / Ouliana Panova / Jesper M Mathiesen / Georgios Skiniotis / ![]() ![]() Abstract: Stimulation of the metabotropic GABA receptor by γ-aminobutyric acid (GABA) results in prolonged inhibition of neurotransmission, which is central to brain physiology. GABA belongs to family C of ...Stimulation of the metabotropic GABA receptor by γ-aminobutyric acid (GABA) results in prolonged inhibition of neurotransmission, which is central to brain physiology. GABA belongs to family C of the G-protein-coupled receptors, which operate as dimers to transform synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins. However, GABA is unique in its function as an obligate heterodimer in which agonist binding and G-protein activation take place on distinct subunits. Here we present cryo-electron microscopy structures of heterodimeric and homodimeric full-length GABA receptors. Complemented by cellular signalling assays and atomistic simulations, these structures reveal that extracellular loop 2 (ECL2) of GABA has an essential role in relaying structural transitions by ordering the linker that connects the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of each of the subunits of GABA caps and interacts with the hydrophilic head of a phospholipid that occupies the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G proteins. These results provide a starting framework through which to decipher the mechanistic modes of signal transduction mediated by GABA dimers, and have important implications for rational drug design that targets these receptors. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 245.8 KB | Display | ![]() |
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PDB format | ![]() | 189.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 21533MC ![]() 6w2yC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Gamma-aminobutyric acid type B receptor subunit ... , 2 types, 2 molecules AB
#1: Protein | Mass: 94173.570 Da / Num. of mol.: 1 / Fragment: UNP residues 30-844 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 102799.164 Da / Num. of mol.: 1 / Fragment: UNP residues 42-941 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Sugars , 2 types, 4 molecules ![](data/chem/img/NAG.gif)
#3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Sugar | |
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-Non-polymers , 3 types, 4 molecules ![](data/chem/img/L9Q.gif)
![](data/chem/img/SGG.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/SGG.gif)
![](data/chem/img/MG.gif)
#5: Chemical | #6: Chemical | ChemComp-SGG / [( | #7: Chemical | ChemComp-MG / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: GABAB Heterodimer / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.5 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid type: Quantifoil R1.2/1.3 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 291 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Average exposure time: 3.5 sec. / Electron dose: 60.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
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Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2601040 | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 286140 / Symmetry type: POINT |