|Entry||Database: PDB / ID: 6w2y|
|Title||CryoEM Structure of GABAB1b Homodimer|
|Components||Gamma-aminobutyric acid type B receptor subunit 1|
|Keywords||SIGNALING PROTEIN / Inhibitor / Homodimer / GPCR|
|Function / homology|
Function and homology information
G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / neuron-glial cell signaling / G protein-coupled receptor heterodimeric complex / G protein-coupled GABA receptor activity / gamma-aminobutyric acid signaling pathway / GABA-ergic synapse / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Schaffer collateral - CA1 synapse / presynaptic membrane / transmembrane signaling receptor activity ...G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential / neuron-glial cell signaling / G protein-coupled receptor heterodimeric complex / G protein-coupled GABA receptor activity / gamma-aminobutyric acid signaling pathway / GABA-ergic synapse / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Schaffer collateral - CA1 synapse / presynaptic membrane / transmembrane signaling receptor activity / postsynaptic membrane / G protein-coupled receptor signaling pathway / dendrite / integral component of plasma membrane / extracellular region / plasma membrane / cytoplasm
Sushi/SCR/CCP superfamily / Periplasmic binding protein-like I / GPCR family 3, C-terminal / GPCR family 3, GABA-B receptor / Receptor, ligand binding region / Sushi/SCR/CCP domain
Gamma-aminobutyric acid type B receptor subunit 1
|Biological species||Homo sapiens (human)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å|
|Authors||Papasergi-Scott, M.M. / Robertson, M.J. / Skiniotis, G.|
|Funding support|| United States, 1items |
|Citation||Journal: Nature / Year: 2020|
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: GABA (γ-aminobutyric acid) stimulation of the metabotropic GABA receptor results in prolonged inhibition of neurotransmission that is central to brain physiology. GABA belongs to the Family C of G ...GABA (γ-aminobutyric acid) stimulation of the metabotropic GABA receptor results in prolonged inhibition of neurotransmission that is central to brain physiology. GABA belongs to the Family C of G protein-coupled receptors (GPCRs), which operate as dimers to relay synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins. GABA, however, is unique in its function as an obligate heterodimer in which agonist binding and G protein activation take place on distinct subunits. Here we show structures of heterodimeric and homodimeric full-length GABA receptors. Complemented by cellular signaling assays and atomistic simulations, the structures reveal an essential role for the GABA extracellular loop 2 (ECL2) in relaying structural transitions by ordering the linker connecting the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of both GABA subunits caps and interacts with the hydrophilic head of a phospholipid occupying the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G protein. These results provide a starting framework to decipher mechanistic modes of signal transduction mediated by GABA dimers and have important implications for rational drug design targeting these receptors.
SummaryFull reportAbout validation report
|Structure viewer||Molecule: |
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A: Gamma-aminobutyric acid type B receptor subunit 1
B: Gamma-aminobutyric acid type B receptor subunit 1
Mass: 94173.570 Da / Num. of mol.: 2 / Fragment: UNP residues 30-844
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GABBR1, GPRC3A / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9UBS5
|#3: Chemical||#4: Chemical||#5: Chemical||Has ligand of interest||N|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction|
|Component||Name: GABAB1b Homodimer / Type: COMPLEX / Entity ID: 1 / Source: RECOMBINANT|
|Molecular weight||Experimental value: NO|
|Source (natural)||Organism: Homo sapiens (human)|
|Source (recombinant)||Organism: Spodoptera frugiperda (fall armyworm)|
|Buffer solution||pH: 7.5|
|Specimen||Conc.: 5 mg/ml / 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|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: TFS KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 130000 X / C2 aperture diameter: 50 µm|
|Image recording||Average exposure time: 8 sec. / Electron dose: 49.7 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|Image scans||Movie frames/image: 40|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|Symmetry||Point symmetry: C1 (asymmetric)|
|3D reconstruction||Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 282811 / Symmetry type: POINT|
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