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Yorodumi- PDB-6n7g: Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form I) -
+Open data
-Basic information
Entry | Database: PDB / ID: 6n7g | |||||||||
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Title | Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form I) | |||||||||
Components |
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Keywords | PROTEIN BINDING / Receptor / RND family | |||||||||
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) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.8 Å | |||||||||
Authors | Yan, N. / Gong, X. / Qian, H.W. | |||||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2019 Title: Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm. Authors: Hongwu Qian / Pingping Cao / Miaohui Hu / Shuai Gao / Nieng Yan / Xin Gong / Abstract: The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of ...The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of signaling cascades. Here, we report the cryo-EM structure of tetrameric Ptch1 in complex with the palmitoylated N-terminal signaling domain of human Sonic hedgehog (ShhN) at a 4:2 stoichiometric ratio. The structure shows that four Ptch1 protomers are organized as a loose dimer of dimers. Each dimer binds to one ShhN through two distinct inhibitory interfaces, one mainly through the N-terminal peptide and the palmitoyl moiety of ShhN and the other through the Ca-mediated interface on ShhN. Map comparison reveals that the cholesteryl moiety of native ShhN occupies a recently identified extracellular steroid binding pocket in Ptch1. Our structure elucidates the tetrameric assembly of Ptch1 and suggests an asymmetric mode of action of the Hh ligands for inhibiting the potential cholesterol transport activity of Ptch1. | |||||||||
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 | 6n7g.cif.gz | 803 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6n7g.ent.gz | 645.3 KB | Display | PDB format |
PDBx/mmJSON format | 6n7g.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/n7/6n7g ftp://data.pdbj.org/pub/pdb/validation_reports/n7/6n7g | HTTPS FTP |
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-Related structure data
Related structure data | 0355MC 0356C 0358C 6n7hC 6n7kC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10456 (Title: Tetrameric Ptch1 complexed with ShhNp / Data size: 8.9 TB Data #1: Oligomeric complex of Ptch1 and Shhp [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 6 molecules ABDECF
#1: Protein | Mass: 150189.578 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTCH1, PTCH / Production host: Homo sapiens (human) / References: UniProt: Q13635 #2: Protein | Mass: 19594.039 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SHH / Production host: Homo sapiens (human) / References: UniProt: Q15465 |
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-Sugars , 2 types, 24 molecules
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #4: Sugar | ChemComp-NAG / |
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-Non-polymers , 4 types, 18 molecules
#5: Chemical | ChemComp-CLR / #6: Chemical | #7: Chemical | ChemComp-CA / #8: Chemical | |
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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
Component | Name: Patch1 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 8 |
Specimen | Conc.: 15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | 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 |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | |||||||||||||||
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EM software |
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CTF correction | Type: NONE | |||||||||||||||
3D reconstruction | Resolution: 6.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 39503 / Symmetry type: POINT |