+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22119 | |||||||||
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Title | Structure of human SMO-Gi complex with SAG | |||||||||
Map data | Structure of human SMO-Gi complex | |||||||||
Sample |
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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 / 9+0 non-motile cilium / central nervous system neuron differentiation / 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 / 9+0 non-motile cilium / central nervous system neuron differentiation / regulation of somatic stem cell population maintenance / pancreas morphogenesis / epithelial-mesenchymal cell signaling / : / myoblast migration / atrial septum morphogenesis / determination of left/right asymmetry in lateral mesoderm / contact inhibition / spinal cord dorsal/ventral patterning / left/right axis specification / ciliary tip / Activation of SMO / thalamus development / patched binding / somite development / positive regulation of branching involved in ureteric bud morphogenesis / type B pancreatic cell development / forebrain morphogenesis / dorsal/ventral neural tube patterning / cellular response to cholesterol / 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 / commissural neuron axon guidance / dopaminergic neuron differentiation / 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 / anterior/posterior pattern specification / ciliary membrane / positive regulation of mesenchymal cell proliferation / negative regulation of epithelial cell differentiation / smoothened signaling pathway / midgut development / 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 / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / endoplasmic reticulum-Golgi intermediate compartment / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / vasculogenesis / 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 / G protein-coupled receptor binding / positive regulation of epithelial cell proliferation / G protein-coupled receptor activity / astrocyte activation / Hedgehog 'on' state / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / multicellular organism growth / 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 / Sensory perception of sweet, bitter, and umami (glutamate) taste / cerebral cortex development / response to peptide hormone Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.96 Å | |||||||||
Authors | Qi X / Li X | |||||||||
Citation | Journal: Nat Chem Biol / Year: 2020 Title: Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling. Authors: Xiaofeng Qi / Lucas Friedberg / Ryan De Bose-Boyd / Tao Long / Xiaochun Li / Abstract: Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain ...Smoothened (SMO), a class Frizzled G protein-coupled receptor (class F GPCR), transduces the Hedgehog signal across the cell membrane. Sterols can bind to its extracellular cysteine-rich domain (CRD) and to several sites in the seven transmembrane helices (7-TMs) of SMO. However, the mechanism by which sterols regulate SMO via multiple sites is unknown. Here we determined the structures of SMO-G complexes bound to the synthetic SMO agonist (SAG) and to 24(S),25-epoxycholesterol (24(S),25-EC). A novel sterol-binding site in the extracellular extension of TM6 was revealed to connect other sites in 7-TMs and CRD, forming an intramolecular sterol channel from the middle side of 7-TMs to CRD. Additional structures of two gain-of-function variants, SMO and SMO, showed that blocking the channel at its midpoints allows sterols to occupy the binding sites in 7-TMs, thereby activating SMO. These data indicate that sterol transport through the core of SMO is a major regulator of SMO-mediated signaling. | |||||||||
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_22119.map.gz | 164.1 MB | EMDB map data format | |
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Header (meta data) | emd-22119-v30.xml emd-22119.xml | 21.1 KB 21.1 KB | Display Display | EMDB header |
Images | emd_22119.png | 29.5 KB | ||
Masks | emd_22119_msk_1.map | 178 MB | Mask map | |
Others | emd_22119_half_map_1.map.gz emd_22119_half_map_2.map.gz | 140.8 MB 140.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22119 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22119 | HTTPS FTP |
-Related structure data
Related structure data | 6xblMC 6xbjC 6xbkC 6xbmC 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_22119.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of human SMO-Gi complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.66 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_22119_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Structure of human SMO-Gi complex
File | emd_22119_half_map_1.map | ||||||||||||
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Annotation | Structure of human SMO-Gi complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Structure of human SMO-Gi complex
File | emd_22119_half_map_2.map | ||||||||||||
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Annotation | Structure of human SMO-Gi complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : hSMO-Gi-SAG
+Supramolecule #1: hSMO-Gi-SAG
+Supramolecule #2: hSMO
+Supramolecule #3: Gi
+Supramolecule #4: scFv16
+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: scFv16
+Macromolecule #6: 3-chloro-N-[trans-4-(methylamino)cyclohexyl]-N-{[3-(pyridin-4-yl)...
+Macromolecule #7: CHOLESTEROL
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: NOT APPLICABLE |
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Final angle assignment | Type: NOT APPLICABLE |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.96 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 550527 |