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- PDB-6n7g: Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form I) -
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Open data
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Basic information
Entry | Database: PDB / ID: 6n7g | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Title | Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form I) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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![]() | PROTEIN BINDING / Receptor / RND family | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Function / homology | ![]() regulation of nodal signaling pathway / neural plate axis specification / response to chlorate / 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 ...regulation of nodal signaling pathway / neural plate axis specification / response to chlorate / 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 / cell proliferation involved in metanephros development / neural tube patterning / 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 / formation of anatomical boundary / smoothened binding / positive regulation of striated muscle cell differentiation / regulation of glial cell proliferation / 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 / salivary gland cavitation / negative regulation of cholesterol efflux / spinal cord dorsal/ventral patterning / negative regulation of mesenchymal cell apoptotic process / determination of left/right asymmetry in lateral mesoderm / epidermal cell fate specification / cell development / spinal cord motor neuron differentiation / negative regulation of T cell differentiation in thymus / positive regulation of T cell differentiation in thymus / establishment of epithelial cell polarity / skeletal muscle cell proliferation / prostate gland development / intermediate filament organization / limb bud formation / stem cell development / embryonic skeletal system development / skeletal muscle fiber differentiation / positive regulation of cerebellar granule cell precursor proliferation / Activation of SMO / limb morphogenesis / mesenchymal cell apoptotic process / patched binding / animal organ formation / negative regulation of cell division / hindbrain development / embryonic digestive tract morphogenesis / positive regulation of skeletal muscle tissue development / somite development / ectoderm development / embryonic foregut morphogenesis / epithelial cell proliferation involved in salivary gland morphogenesis / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / neuron fate commitment / cerebellar granule cell precursor proliferation / positive regulation of immature T cell proliferation in thymus / lymphoid progenitor cell differentiation / dorsal/ventral neural tube patterning / self proteolysis / lung lobe morphogenesis / smooth muscle tissue development / artery development / positive regulation of astrocyte differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative thymic T cell selection / pharyngeal system development / cellular response to cholesterol / 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 / branching involved in salivary gland morphogenesis Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.8 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
![]() | Yan, N. / Gong, X. / Qian, H.W. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 812 KB | Display | ![]() |
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PDB format | ![]() | 645.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.8 MB | Display | ![]() |
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Full document | ![]() | 1.8 MB | Display | |
Data in XML | ![]() | 118.2 KB | Display | |
Data in CIF | ![]() | 178.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 0355MC ![]() 0356C ![]() 0358C ![]() 6n7hC ![]() 6n7kC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Oligomeric complex of Ptch1 and Shhp [micrographs - multiframe]) |
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Links
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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.) ![]() ![]() #2: Protein | Mass: 19594.039 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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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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-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
Component | Name: Patch1 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
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 |
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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 |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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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 |