+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20190 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of human Smoothened-Gi complex | |||||||||
Map data | Smoothened-Gi complex | |||||||||
Sample |
| |||||||||
Function / homology | Function and homology information ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / regulation of heart morphogenesis / negative regulation of hair follicle development / central nervous system neuron differentiation / 9+0 non-motile cilium / regulation of somatic stem cell population maintenance / pancreas morphogenesis / epithelial-mesenchymal cell signaling / : ...ventral midline determination / mesenchymal to epithelial transition involved in metanephric renal vesicle formation / regulation of heart morphogenesis / negative regulation of hair follicle development / central nervous system neuron differentiation / 9+0 non-motile cilium / regulation of somatic stem cell population maintenance / pancreas morphogenesis / epithelial-mesenchymal cell signaling / : / myoblast migration / atrial septum morphogenesis / contact inhibition / determination of left/right asymmetry in lateral mesoderm / spinal cord dorsal/ventral patterning / left/right axis specification / ciliary tip / Activation of SMO / patched binding / thalamus development / somite development / positive regulation of branching involved in ureteric bud morphogenesis / type B pancreatic cell development / forebrain morphogenesis / cellular response to cholesterol / dorsal/ventral neural tube patterning / BBSome-mediated cargo-targeting to cilium / positive regulation of organ growth / smooth muscle tissue development / pattern specification process / cerebellar cortex morphogenesis / mammary gland epithelial cell differentiation / dentate gyrus development / positive regulation of multicellular organism growth / dopaminergic neuron differentiation / commissural neuron axon guidance / oxysterol binding / positive regulation of smoothened signaling pathway / Class B/2 (Secretin family receptors) / cell fate specification / neural crest cell migration / cAMP-dependent protein kinase inhibitor activity / ciliary membrane / positive regulation of mesenchymal cell proliferation / anterior/posterior pattern specification / negative regulation of epithelial cell differentiation / midgut development / smoothened signaling pathway / hair follicle morphogenesis / positive regulation of neuroblast proliferation / heart looping / negative regulation of DNA binding / odontogenesis of dentin-containing tooth / protein kinase A catalytic subunit binding / neuroblast proliferation / endoplasmic reticulum-Golgi intermediate compartment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / vasculogenesis / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / Hedgehog 'off' state / skeletal muscle fiber development / homeostasis of number of cells within a tissue / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / centriole / protein sequestering activity / negative regulation of protein phosphorylation / epithelial cell proliferation / central nervous system development / Regulation of insulin secretion / positive regulation of epithelial cell proliferation / G protein-coupled receptor binding / G protein-coupled receptor activity / astrocyte activation / Hedgehog 'on' state / Olfactory Signaling Pathway / multicellular organism growth / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / cilium / 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) / cerebral cortex development / Sensory perception of sweet, bitter, and umami (glutamate) taste Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / Resolution: 3.84 Å | |||||||||
Authors | Qi X / Li X | |||||||||
Citation | Journal: Nature / Year: 2019 Title: Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric G. Authors: Xiaofeng Qi / Heng Liu / Bonne Thompson / Jeffrey McDonald / Cheng Zhang / Xiaochun Li / Abstract: The oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of the Frizzled-class (class-F), transduces the Hedgehog signal from the tumour suppressor Patched-1 (PTCH1) to the glioma- ...The oncoprotein Smoothened (SMO), a G-protein-coupled receptor (GPCR) of the Frizzled-class (class-F), transduces the Hedgehog signal from the tumour suppressor Patched-1 (PTCH1) to the glioma-associated-oncogene (GLI) transcription factors, which activates the Hedgehog signalling pathway. It has remained unknown how PTCH1 modulates SMO, how SMO is stimulated to form a complex with heterotrimeric G proteins and whether G-protein coupling contributes to the activation of GLI proteins. Here we show that 24,25-epoxycholesterol, which we identify as an endogenous ligand of PTCH1, can stimulate Hedgehog signalling in cells and can trigger G-protein signalling via human SMO in vitro. We present a cryo-electron microscopy structure of human SMO bound to 24(S),25-epoxycholesterol and coupled to a heterotrimeric G protein. The structure reveals a ligand-binding site for 24(S),25-epoxycholesterol in the 7-transmembrane region, as well as a G-coupled activation mechanism of human SMO. Notably, the G protein presents a different arrangement from that of class-A GPCR-G complexes. Our work provides molecular insights into Hedgehog signal transduction and the activation of a class-F GPCR. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20190.map.gz | 78.3 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-20190-v30.xml emd-20190.xml | 18.5 KB 18.5 KB | Display Display | EMDB header |
Images | emd_20190.png | 58.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20190 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20190 | HTTPS FTP |
-Related structure data
Related structure data | 6ot0MC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_20190.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Smoothened-Gi complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
+Entire : Smoothened-Gi-Fab complex
+Supramolecule #1: Smoothened-Gi-Fab complex
+Supramolecule #2: Smoothened homolog
+Supramolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine ...
+Supramolecule #4: Fab light chain, Fab heavy chain
+Macromolecule #1: Smoothened homolog
+Macromolecule #2: Guanine nucleotide-binding protein G(i) subunit alpha-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #5: Fab light chain
+Macromolecule #6: Fab heavy chain
+Macromolecule #7: 17-[3-(3,3-DIMETHYL-OXIRANYL)-1-METHYL-PROPYL]-10,13-DIMETHYL-2,3...
-Experimental details
-Structure determination
Processing | single particle reconstruction |
---|---|
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.4 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | #0 - Type of model: EMDB MAP #0 - EMDB ID: #1 - Type of model: PDB ENTRY #1 - PDB model - PDB ID: #2 - Type of model: PDB ENTRY #2 - PDB model - PDB ID: |
---|---|
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.84 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 141100 |