+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31049 | |||||||||
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Title | Cryo-EM structure of human GABA(B) receptor-Gi protein complex | |||||||||
Map data | Local refinement composite map of GABAB-Gi complex | |||||||||
Sample |
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Function / homology | Function and homology information 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 / positive regulation of glutamate secretion / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / axolemma / GABA-ergic synapse / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / dendritic shaft / Regulation of insulin secretion / G protein-coupled receptor binding / mitochondrial membrane / response to nicotine / G-protein beta/gamma-subunit complex binding / Schaffer collateral - CA1 synapse / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / osteoblast differentiation / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / transmembrane signaling receptor activity / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / synaptic vesicle / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / presynaptic membrane / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / postsynaptic membrane / response to ethanol / cell cycle / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / dendritic spine / neuron projection Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Shen C / Mao C / Xu C / Jin N / Zhang H / Shen D / Shen Q / Wang X / Hou T / Rondard P ...Shen C / Mao C / Xu C / Jin N / Zhang H / Shen D / Shen Q / Wang X / Hou T / Rondard P / Chen Z / Pin J / Zhang Y / Liu J | |||||||||
Citation | Journal: Nature / Year: 2021 Title: Structural basis of GABA receptor-G protein coupling. Authors: Cangsong Shen / Chunyou Mao / Chanjuan Xu / Nan Jin / Huibing Zhang / Dan-Dan Shen / Qingya Shen / Xiaomei Wang / Tingjun Hou / Zhong Chen / Philippe Rondard / Jean-Philippe Pin / Yan Zhang / Jianfeng Liu / Abstract: G-protein-coupled receptors (GPCRs) have central roles in intercellular communication. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is ...G-protein-coupled receptors (GPCRs) have central roles in intercellular communication. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABA receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with G protein. We found that a single G protein interacts with the GB2 subunit of the GABA receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABA receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_31049.map.gz | 105.7 MB | EMDB map data format | |
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Header (meta data) | emd-31049-v30.xml emd-31049.xml | 28.2 KB 28.2 KB | Display Display | EMDB header |
Images | emd_31049.png | 85.4 KB | ||
Others | emd_31049_additional_1.map.gz emd_31049_additional_2.map.gz | 106.3 MB 23.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31049 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31049 | HTTPS FTP |
-Validation report
Summary document | emd_31049_validation.pdf.gz | 309 KB | Display | EMDB validaton report |
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Full document | emd_31049_full_validation.pdf.gz | 308.5 KB | Display | |
Data in XML | emd_31049_validation.xml.gz | 6.5 KB | Display | |
Data in CIF | emd_31049_validation.cif.gz | 7.5 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31049 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-31049 | HTTPS FTP |
-Related structure data
Related structure data | 7eb2MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31049.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Local refinement composite map of GABAB-Gi complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: Local refinement map of GABAB receptor
File | emd_31049_additional_1.map | ||||||||||||
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Annotation | Local refinement map of GABAB receptor | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Local refinement map of Gil protein
File | emd_31049_additional_2.map | ||||||||||||
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Annotation | Local refinement map of Gil protein | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : The GABAB-Gi1 complex
+Supramolecule #1: The GABAB-Gi1 complex
+Supramolecule #2: Guanine nucleotide-binding protein
+Supramolecule #3: ScFv16
+Supramolecule #4: Gamma-aminobutyric acid type B receptor
+Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: ScFv16
+Macromolecule #5: Gamma-aminobutyric acid type B receptor subunit 1
+Macromolecule #6: Gamma-aminobutyric acid type B receptor subunit 2
+Macromolecule #7: baclofen
+Macromolecule #8: (3S)-5,7-ditert-butyl-3-oxidanyl-3-(trifluoromethyl)-1-benzofuran...
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1.8 mg/mL | ||||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE | ||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Frames/image: 1-40 / Number real images: 13843 / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Calibrated magnification: 49310 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal magnification: 29000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |