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Open data
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Basic information
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Title | Cryo-EM structure of GPR156-miniGo-scFv16 complex | |||||||||
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![]() | Membrane protein / G-protein coupled receptor / Signal transduction / Phospholipid | |||||||||
Function / homology | ![]() G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / gamma-aminobutyric acid signaling pathway / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding ...G protein-coupled GABA receptor activity / G protein-coupled receptor heterodimeric complex / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / vesicle docking involved in exocytosis / gamma-aminobutyric acid signaling pathway / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / muscle contraction / locomotory behavior / G-protein beta/gamma-subunit complex binding / 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-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / 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 / 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 / GPER1 signaling / 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 / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / Ras protein signal transduction / G alpha (q) signalling events / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.33 Å | |||||||||
![]() | Shin J / Park J / Cho Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Constitutive activation mechanism of a class C GPCR. Authors: Jinwoo Shin / Junhyeon Park / Jieun Jeong / Jordy Homing Lam / Xingyu Qiu / Di Wu / Kuglae Kim / Joo-Youn Lee / Carol V Robinson / Jaekyung Hyun / Vsevolod Katritch / Kwang Pyo Kim / Yunje Cho / ![]() ![]() ![]() Abstract: Class C G-protein-coupled receptors (GPCRs) are activated through binding of agonists to the large extracellular domain (ECD) followed by rearrangement of the transmembrane domains (TMDs). GPR156, a ...Class C G-protein-coupled receptors (GPCRs) are activated through binding of agonists to the large extracellular domain (ECD) followed by rearrangement of the transmembrane domains (TMDs). GPR156, a class C orphan GPCR, is unique because it lacks an ECD and exhibits constitutive activity. Impaired GPR156-G signaling contributes to loss of hearing. Here we present the cryo-electron microscopy structures of human GPR156 in the G-free and G-coupled states. We found that an endogenous phospholipid molecule is located within each TMD of the GPR156 dimer. Asymmetric binding of Gα to the phospholipid-bound GPR156 dimer restructures the first and second intracellular loops and the carboxy-terminal part of the elongated transmembrane 7 (TM7) without altering dimer conformation. Our findings reveal that GPR156 is a transducer for phospholipid signaling. Constant binding of abundant phospholipid molecules and the G-protein-induced reshaping of the cytoplasmic face provide a basis for the constitutive activation of GPR156. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 248.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21.1 KB 21.1 KB | Display Display | ![]() |
Images | ![]() | 127.6 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Others | ![]() ![]() | 243.8 MB 243.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8iedMC ![]() 8iebC ![]() 8iecC ![]() 8ieiC ![]() 8iepC ![]() 8ieqC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.81 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_35380_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35380_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
+Entire : GPR156-miniGo-scFv16 complex
+Supramolecule #1: GPR156-miniGo-scFv16 complex
+Supramolecule #2: GPR156
+Supramolecule #3: miniGo heterotrimeric complex
+Supramolecule #4: scFv16
+Macromolecule #1: Probable G-protein coupled receptor 156
+Macromolecule #2: Guanine nucleotide-binding protein G(o) subunit alpha
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Single-chain variable fragment scFv16
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: [(2R)-3-[(E)-hexadec-9-enoyl]oxy-2-octadecanoyloxy-propyl] 2-(tri...
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER Details: GPR156: AlphaFold2 G-protein and scFv16: 7UM5 (PDB) |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.33 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 205728 |
Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |