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- PDB-6rmg: Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II -
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Basic information
Entry | Database: PDB / ID: 6rmg | |||||||||
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Title | Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II | |||||||||
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![]() | MEMBRANE PROTEIN / Patched / PTCH1 / Hedgehog / ShhN | |||||||||
Function / homology | ![]() regulation of nodal signaling pathway / neural plate axis specification / cell differentiation involved in kidney development / 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 ...regulation of nodal signaling pathway / neural plate axis specification / cell differentiation involved in kidney development / 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 / hedgehog receptor activity / response to chlorate / neural tube patterning / cell proliferation involved in metanephros development / trunk neural crest cell migration / Formation of lateral plate mesoderm / hindgut morphogenesis / polarity specification of anterior/posterior axis / negative regulation of alpha-beta T cell differentiation / regulation of prostatic bud formation / regulation of glial cell proliferation / formation of anatomical boundary / smoothened binding / positive regulation of striated muscle cell differentiation / metanephric mesenchymal cell proliferation involved in metanephros development / ventral midline development / trachea morphogenesis / hedgehog family protein binding / cholesterol-protein transferase activity / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / bud outgrowth involved in lung branching / epithelial-mesenchymal cell signaling / hindlimb morphogenesis / Ligand-receptor interactions / laminin-1 binding / lung epithelium development / negative regulation of cholesterol efflux / salivary gland cavitation / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / negative regulation of mesenchymal cell apoptotic process / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / epidermal cell fate specification / cell development / spinal cord motor neuron differentiation / positive regulation of T cell differentiation in thymus / establishment of epithelial cell polarity / prostate gland development / intermediate filament organization / cerebellar granule cell precursor proliferation / limb bud formation / embryonic skeletal system development / skeletal muscle fiber differentiation / lung lobe morphogenesis / limb morphogenesis / Activation of SMO / mesenchymal cell apoptotic process / negative regulation of cell division / patched binding / animal organ formation / embryonic digestive tract morphogenesis / embryonic foregut morphogenesis / hindbrain development / positive regulation of skeletal muscle tissue development / epithelial cell proliferation involved in salivary gland morphogenesis / somite development / ectoderm development / neuron fate commitment / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / skeletal muscle cell proliferation / stem cell development / positive regulation of immature T cell proliferation in thymus / lymphoid progenitor cell differentiation / dorsal/ventral neural tube patterning / self proteolysis / smooth muscle tissue development / artery development / cellular response to cholesterol / positive regulation of astrocyte differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative thymic T cell selection / thalamus development / pharyngeal system development / pattern specification process / regulation of stem cell proliferation / mammary gland duct morphogenesis / mammary gland epithelial cell differentiation / positive regulation of epithelial cell proliferation involved in prostate gland development / male genitalia development Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Korkhov, V.M. / Qi, C. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of sterol recognition by human hedgehog receptor PTCH1. Authors: Chao Qi / Giulio Di Minin / Irene Vercellino / Anton Wutz / Volodymyr M Korkhov / ![]() Abstract: Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog ...Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4-Å cryo-EM structure of the human PTCH1 bound to ShhN, a modified hedgehog ligand mimicking its palmitoylated form. The membrane-embedded part of PTCH1 is surrounded by 10 sterol molecules at the inner and outer lipid bilayer portion of the protein. The annular sterols interact at multiple sites with both the sterol-sensing domain (SSD) and the SSD-like domain (SSDL), which are located on opposite sides of PTCH1. The structure reveals a possible route for sterol translocation across the lipid bilayer by PTCH1 and homologous transporters. | |||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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PDBx/mmCIF format | ![]() | 441.5 KB | Display | ![]() |
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PDB format | ![]() | 358.8 KB | Display | ![]() |
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-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 49.1 KB | Display | |
Data in CIF | ![]() | 71.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4936MC ![]() 4939C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 163846.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() Gene: PTCH1, PTCH, EAH_00062270 / Plasmid: pACMV / Cell line (production host): HEK293S GnTI- / Production host: ![]() |
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#2: Protein | Mass: 32397.508 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Sugars , 2 types, 6 molecules 
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
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#4: Sugar | ChemComp-NAG / |
-Non-polymers , 2 types, 12 molecules 


#5: Chemical | ChemComp-Y01 / #6: Chemical | ChemComp-ZN / | |
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-Details
Has protein modification | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Specimen support | Grid material: GOLD | ||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: -2400 nm / Nominal defocus min: -800 nm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 44.7 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.11.1_2575: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 707620 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 200679 / Num. of class averages: 1 / Symmetry type: POINT |