+Open data
-Basic information
Entry | Database: PDB / ID: 6oeu | ||||||||||||
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Title | Structure of human Patched1 | ||||||||||||
Components | Protein patched homolog 1 | ||||||||||||
Keywords | MEMBRANE PROTEIN / tumor suppressor | ||||||||||||
Function / homology | Function and homology information neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / neural tube patterning / cell proliferation involved in metanephros development / smoothened binding / hedgehog family protein binding / Ligand-receptor interactions / hindlimb morphogenesis ...neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / neural tube patterning / cell proliferation involved in metanephros development / smoothened binding / hedgehog family protein binding / Ligand-receptor interactions / hindlimb morphogenesis / epidermal cell fate specification / spinal cord motor neuron differentiation / Activation of SMO / prostate gland development / limb morphogenesis / somite development / patched binding / negative regulation of cell division / cellular response to cholesterol / dorsal/ventral neural tube patterning / smooth muscle tissue development / pharyngeal system development / mammary gland duct morphogenesis / mammary gland epithelial cell differentiation / cell fate determination / commissural neuron axon guidance / metanephric collecting duct development / regulation of smoothened signaling pathway / dorsal/ventral pattern formation / Hedgehog 'off' state / Class B/2 (Secretin family receptors) / embryonic limb morphogenesis / ciliary membrane / negative regulation of multicellular organism growth / branching involved in ureteric bud morphogenesis / cholesterol binding / smoothened signaling pathway / positive regulation of epidermal cell differentiation / dendritic growth cone / spermatid development / keratinocyte proliferation / positive regulation of cholesterol efflux / negative regulation of keratinocyte proliferation / negative regulation of osteoblast differentiation / embryonic organ development / axonal growth cone / heart morphogenesis / response to retinoic acid / negative regulation of stem cell proliferation / response to mechanical stimulus / negative regulation of smoothened signaling pathway / regulation of mitotic cell cycle / cyclin binding / stem cell proliferation / neural tube closure / protein localization to plasma membrane / liver regeneration / animal organ morphogenesis / Hedgehog 'on' state / negative regulation of DNA-binding transcription factor activity / brain development / caveola / protein processing / endocytic vesicle membrane / apical part of cell / response to estradiol / glucose homeostasis / regulation of protein localization / heparin binding / midbody / in utero embryonic development / response to xenobiotic stimulus / intracellular membrane-bounded organelle / protein-containing complex binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / Resolution: 3.5 Å | ||||||||||||
Authors | Qi, X. / Li, X. / Wang, J. | ||||||||||||
Citation | Journal: Nature / Year: 2018 Title: Structures of human Patched and its complex with native palmitoylated sonic hedgehog. Authors: Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Jiawei Wang / Xiaochun Li / Abstract: Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms. Whereas deficient HH signalling leads to birth defects, unrestrained HH ...Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms. Whereas deficient HH signalling leads to birth defects, unrestrained HH signalling is implicated in human cancers. N-terminally palmitoylated HH releases the repression of Patched to the oncoprotein smoothened (SMO); however, the mechanism by which HH recognizes Patched is unclear. Here we report cryo-electron microscopy structures of human patched 1 (PTCH1) alone and in complex with the N-terminal domain of 'native' sonic hedgehog (native SHH-N has both a C-terminal cholesterol and an N-terminal fatty-acid modification), at resolutions of 3.5 Å and 3.8 Å, respectively. The structure of PTCH1 has internal two-fold pseudosymmetry in the transmembrane core, which features a sterol-sensing domain and two homologous extracellular domains, resembling the architecture of Niemann-Pick C1 (NPC1) protein. The palmitoylated N terminus of SHH-N inserts into a cavity between the extracellular domains of PTCH1 and dominates the PTCH1-SHH-N interface, which is distinct from that reported for SHH-N co-receptors. Our biochemical assays show that SHH-N may use another interface, one that is required for its co-receptor binding, to recruit PTCH1 in the absence of a covalently attached palmitate. Our work provides atomic insights into the recognition of the N-terminal domain of HH (HH-N) by PTCH1, offers a structural basis for cooperative binding of HH-N to various receptors and serves as a molecular framework for HH signalling and its malfunction in disease. | ||||||||||||
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 | 6oeu.cif.gz | 207.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6oeu.ent.gz | 154.1 KB | Display | PDB format |
PDBx/mmJSON format | 6oeu.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6oeu_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6oeu_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6oeu_validation.xml.gz | 31.6 KB | Display | |
Data in CIF | 6oeu_validation.cif.gz | 46.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/oe/6oeu ftp://data.pdbj.org/pub/pdb/validation_reports/oe/6oeu | HTTPS FTP |
-Related structure data
Related structure data | 7795MC 7796C 6oevC 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: 161711.406 Da / Num. of mol.: 1 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 |
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#2: 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 |
-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: 0.121 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: 5.8.0238 / 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: 789118 / Symmetry type: POINT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.5→78.2 Å / Cor.coef. Fo:Fc: 0.772 / SU B: 82.336 / SU ML: 1.098 / ESU R: 1.691 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: 120.582 Å2
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Refinement step | Cycle: 1 / Total: 7206 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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