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Yorodumi- PDB-6rmg: Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II -
+Open data
-Basic information
Entry | Database: PDB / ID: 6rmg | |||||||||
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Title | Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / Patched / PTCH1 / Hedgehog / ShhN | |||||||||
Function / homology | Function and homology information Formation of lateral plate mesoderm / positive regulation of skeletal muscle cell proliferation / neural plate axis specification / 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 ...Formation of lateral plate mesoderm / positive regulation of skeletal muscle cell proliferation / neural plate axis specification / 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 / cell differentiation involved in kidney development / positive regulation of mesenchymal cell proliferation involved in ureter development / polarity specification of anterior/posterior axis / trunk neural crest cell migration / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / 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 / smoothened binding / neural tube patterning / formation of anatomical boundary / lung epithelium development / positive regulation of striated muscle cell differentiation / ventral midline development / hedgehog family protein binding / 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 / hindlimb morphogenesis / salivary gland cavitation / negative regulation of cholesterol efflux / determination of left/right asymmetry in lateral mesoderm / spinal cord dorsal/ventral patterning / negative regulation of mesenchymal cell apoptotic process / positive regulation of cerebellar granule cell precursor proliferation / cell development / negative regulation of T cell differentiation in thymus / epidermal cell fate specification / spinal cord motor neuron differentiation / positive regulation of T cell differentiation in thymus / intermediate filament organization / cerebellar granule cell precursor proliferation / mesenchymal cell apoptotic process / embryonic skeletal system development / prostate gland development / establishment of epithelial cell polarity / limb bud formation / lung lobe morphogenesis / Activation of SMO / negative regulation of cell division / skeletal muscle fiber differentiation / thalamus development / embryonic foregut morphogenesis / patched binding / limb morphogenesis / embryonic digestive tract morphogenesis / somite development / hindbrain development / negative thymic T cell selection / positive regulation of skeletal muscle tissue development / ectoderm development / epithelial cell proliferation involved in salivary gland morphogenesis / animal organ formation / neuron fate commitment / dorsal/ventral neural tube patterning / stem cell development / mesenchymal cell proliferation involved in lung development / cellular response to cholesterol / negative regulation of dopaminergic neuron differentiation / skeletal muscle cell proliferation / positive regulation of immature T cell proliferation in thymus / oligodendrocyte development / lymphoid progenitor cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / smooth muscle tissue development / male genitalia development / positive regulation of astrocyte differentiation / regulation of stem cell proliferation / pattern specification process / artery development / self proteolysis / epithelial cell proliferation involved in prostate gland development / pharyngeal system development Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Eimeria acervulina (eukaryote) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
Authors | Korkhov, V.M. / Qi, C. | |||||||||
Funding support | Switzerland, 1items
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Citation | Journal: Sci Adv / Year: 2019 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
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6rmg.cif.gz | 434.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6rmg.ent.gz | 358.7 KB | Display | PDB format |
PDBx/mmJSON format | 6rmg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rm/6rmg ftp://data.pdbj.org/pub/pdb/validation_reports/rm/6rmg | HTTPS FTP |
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-Related structure data
Related structure data | 4936MC 4939C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Homo sapiens (human), (gene. exp.) Eimeria acervulina (eukaryote) Gene: PTCH1, PTCH, EAH_00062270 / Plasmid: pACMV / Cell line (production host): HEK293S GnTI- / Production host: Homo sapiens (human) / References: UniProt: Q13635, UniProt: U6GSR1 |
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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.) Homo sapiens (human) / Gene: SHH / Plasmid: pET28a / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q15465 |
-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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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
Source (natural) |
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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 |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy / 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) |
-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 |