+Open data
-Basic information
Entry | Database: PDB / ID: 6e1h | |||||||||
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Title | Structure of 2:1 human Ptch1-Shh-N complex | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / tumor suppressor | |||||||||
Function / homology | Function and homology information 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 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 / neural tube patterning / Formation of lateral plate mesoderm / 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 / 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 / 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 / cell development / positive regulation of cerebellar granule cell precursor proliferation / 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 / 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 / limb morphogenesis / thalamus development / embryonic digestive tract morphogenesis / somite development / patched binding / embryonic foregut morphogenesis / negative regulation of cell division / 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 / cellular response to cholesterol / 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 / pharyngeal system development / epithelial cell proliferation involved in prostate gland development / mammary gland epithelial cell differentiation Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / Resolution: 3.5 Å | |||||||||
Authors | Qi, X. / Li, X. | |||||||||
Citation | Journal: Science / Year: 2018 Title: Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex. Authors: Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Xiaochun Li / Abstract: Aberrant Hedgehog (HH) signaling leads to various types of cancer and birth defects. N-terminally palmitoylated HH initiates signaling by binding its receptor Patched-1 (PTCH1). A recent 1:1 PTCH1-HH ...Aberrant Hedgehog (HH) signaling leads to various types of cancer and birth defects. N-terminally palmitoylated HH initiates signaling by binding its receptor Patched-1 (PTCH1). A recent 1:1 PTCH1-HH complex structure visualized a palmitate-mediated binding site on HH, which was inconsistent with previous studies that implied a distinct, calcium-mediated binding site for PTCH1 and HH co-receptors. Our 3.5-angstrom resolution cryo-electron microscopy structure of native Sonic Hedgehog (SHH-N) in complex with PTCH1 at a physiological calcium concentration reconciles these disparate findings and demonstrates that one SHH-N molecule engages both epitopes to bind two PTCH1 receptors in an asymmetric manner. Functional assays using PTCH1 or SHH-N mutants that disrupt the individual interfaces illustrate that simultaneous engagement of both interfaces is required for efficient signaling in cells. | |||||||||
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 | 6e1h.cif.gz | 386.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6e1h.ent.gz | 306 KB | Display | PDB format |
PDBx/mmJSON format | 6e1h.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6e1h_validation.pdf.gz | 886.9 KB | Display | wwPDB validaton report |
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Full document | 6e1h_full_validation.pdf.gz | 905.1 KB | Display | |
Data in XML | 6e1h_validation.xml.gz | 57.7 KB | Display | |
Data in CIF | 6e1h_validation.cif.gz | 86.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/e1/6e1h ftp://data.pdbj.org/pub/pdb/validation_reports/e1/6e1h | HTTPS FTP |
-Related structure data
Related structure data | 8955MC 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
#1: Protein | Mass: 160714.406 Da / Num. of mol.: 2 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.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SHH / Production host: Homo sapiens (human) / References: UniProt: Q15465 #3: Chemical | ChemComp-ZN / | #4: Chemical | #5: Chemical | ChemComp-PLM / | |
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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: Ptc / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.265 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: NO |
-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: DARK FIELD |
Image recording | Electron dose: 1.6 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: REFMAC / Version: 5.8.0222 / Classification: refinement | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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CTF correction | Type: NONE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 77712 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Cor.coef. Fo:Fc: 0.791 / Highest resolution: 3.5 Å / SU B: 73.029 / SU ML: 0.917 / ESU R: 1.045 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS /
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 80.671 Å2
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Refinement step | Cycle: 1 / Total: 16669 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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