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Yorodumi- EMDB-24466: Cryo-EM structure of Xenopus Patched-1 in complex with GAS1 and S... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-24466 | |||||||||
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Title | Cryo-EM structure of Xenopus Patched-1 in complex with GAS1 and Sonic Hedgehog | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information : / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation ...: / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of kidney smooth muscle cell differentiation / morphogen activity / regulation of odontogenesis / positive regulation of mesenchymal cell proliferation involved in ureter development / polarity specification of anterior/posterior axis / trunk neural crest cell migration / hedgehog receptor activity / Formation of lateral plate mesoderm / hindgut morphogenesis / striated muscle tissue development / negative regulation of alpha-beta T cell differentiation / regulation of glial cell proliferation / regulation of prostatic bud formation / metanephric mesenchymal cell proliferation involved in metanephros development / formation of anatomical boundary / lung epithelium development / positive regulation of striated muscle cell differentiation / ventral midline development / trachea morphogenesis / cholesterol-protein transferase activity / bud outgrowth involved in lung branching / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / epithelial-mesenchymal cell signaling / laminin-1 binding / Ligand-receptor interactions / negative regulation of cholesterol efflux / salivary gland cavitation / spinal cord dorsal/ventral patterning / regulation of ER to Golgi vesicle-mediated transport / determination of left/right asymmetry in lateral mesoderm / negative regulation of mesenchymal cell apoptotic process / cell development / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / spinal cord motor neuron differentiation / positive regulation of T cell differentiation in thymus / cerebellar granule cell precursor proliferation / intermediate filament organization / mesenchymal cell apoptotic process / prostate gland development / embryonic skeletal system development / limb bud formation / lung lobe morphogenesis / Activation of SMO / establishment of epithelial cell polarity / skeletal muscle fiber differentiation / thalamus development / embryonic digestive tract morphogenesis / somite development / patched binding / embryonic foregut morphogenesis / epithelial cell proliferation involved in salivary gland morphogenesis / hindbrain development / animal organ formation / ectoderm development / positive regulation of skeletal muscle tissue development / neuron fate commitment / stem cell development / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / skeletal muscle cell proliferation / negative thymic T cell selection / lymphoid progenitor cell differentiation / positive regulation of immature T cell proliferation in thymus / dorsal/ventral neural tube patterning / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / smooth muscle tissue development / regulation of stem cell proliferation / oligodendrocyte development / male genitalia development / artery development / positive regulation of astrocyte differentiation / pattern specification process / self proteolysis / epithelial cell proliferation involved in prostate gland development / positive regulation of epithelial cell proliferation involved in prostate gland development / embryonic pattern specification / branching involved in salivary gland morphogenesis / Release of Hh-Np from the secreting cell / lung-associated mesenchyme development / Formation of axial mesoderm / regulation of proteolysis / dopaminergic neuron differentiation / intein-mediated protein splicing / positive thymic T cell selection / metanephros development / metanephric collecting duct development Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Xenopus laevis (African clawed frog) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.53 Å | |||||||||
Authors | Huang P / Lian T / Wierbowski B / Garcia-Linares S / Jiang J / Salic A | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Dev Cell / Year: 2022 Title: Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex. Authors: Pengxiang Huang / Bradley M Wierbowski / Tengfei Lian / Charlene Chan / Sara García-Linares / Jiansen Jiang / Adrian Salic / Abstract: The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and ...The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and cancer. SHH engagement with PTCH1 requires the GAS1 coreceptor, but the mechanism is unknown. We demonstrate a unique role for GAS1, catalyzing SHH-PTCH1 complex assembly in vertebrate cells by direct SHH transfer from the extracellular SCUBE2 carrier to PTCH1. Structure of the GAS1-SHH-PTCH1 transition state identifies how GAS1 recognizes the SHH palmitate and cholesterol modifications in modular fashion and how it facilitates lipid-dependent SHH handoff to PTCH1. Structure-guided experiments elucidate SHH movement from SCUBE2 to PTCH1, explain disease mutations, and demonstrate that SHH-induced PTCH1 dimerization causes its internalization from the cell surface. These results define how the signaling-competent SHH-PTCH1 complex assembles, the key step triggering the Hedgehog pathway, and provide a paradigm for understanding morphogen reception and its regulation. | |||||||||
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_24466.map.gz | 33.8 MB | EMDB map data format | |
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Header (meta data) | emd-24466-v30.xml emd-24466.xml | 14.7 KB 14.7 KB | Display Display | EMDB header |
Images | emd_24466.png | 148.5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-24466 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-24466 | HTTPS FTP |
-Validation report
Summary document | emd_24466_validation.pdf.gz | 347.9 KB | Display | EMDB validaton report |
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Full document | emd_24466_full_validation.pdf.gz | 347.4 KB | Display | |
Data in XML | emd_24466_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_24466_validation.cif.gz | 6.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24466 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-24466 | HTTPS FTP |
-Related structure data
Related structure data | 7rhqMC 7rhrC 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_24466.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
+Entire : Patched Hedgehog GAS1 complex
+Supramolecule #1: Patched Hedgehog GAS1 complex
+Macromolecule #1: Patched-1
+Macromolecule #2: Sonic hedgehog protein N-product
+Macromolecule #3: Growth arrest-specific protein 1
+Macromolecule #5: CHOLESTEROL
+Macromolecule #6: CHOLESTEROL HEMISUCCINATE
+Macromolecule #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #8: ZINC ION
+Macromolecule #9: CALCIUM ION
+Macromolecule #10: PALMITIC ACID
-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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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 71.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 100.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.53 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 54175 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |