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Yorodumi- PDB-6mg8: Structural basis for cholesterol transport-like activity of the H... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6mg8 | ||||||||||||||||||
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Title | Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched | ||||||||||||||||||
Components | Protein patched homolog 1 | ||||||||||||||||||
Keywords | MEMBRANE PROTEIN / Receptor Membrane protein | ||||||||||||||||||
Function / homology | Function and homology information Ligand-receptor interactions / Activation of SMO / neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / smoothened binding / neural tube formation / hedgehog family protein binding ...Ligand-receptor interactions / Activation of SMO / neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / smoothened binding / neural tube formation / hedgehog family protein binding / hindlimb morphogenesis / Hedgehog 'on' state / epidermal cell fate specification / spinal cord motor neuron differentiation / prostate gland development / Hedgehog 'off' state / somite development / patched binding / negative regulation of cell division / cellular response to cholesterol / dorsal/ventral neural tube patterning / smooth muscle tissue development / pattern specification process / pharyngeal system development / mammary gland epithelial cell differentiation / mammary gland duct morphogenesis / mammary gland development / cell fate determination / commissural neuron axon guidance / metanephric collecting duct development / dorsal/ventral pattern formation / regulation of growth / embryonic limb morphogenesis / negative regulation of multicellular organism growth / positive regulation of cholesterol efflux / branching involved in ureteric bud morphogenesis / cholesterol binding / negative regulation of osteoblast differentiation / positive regulation of epidermal cell differentiation / regulation of mitotic cell cycle / dendritic growth cone / keratinocyte proliferation / cyclin binding / spermatid development / negative regulation of keratinocyte proliferation / epidermis development / 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 / epithelial cell proliferation / liver regeneration / stem cell proliferation / caveola / neural tube closure / protein localization to plasma membrane / animal organ morphogenesis / brain development / cilium / protein processing / negative regulation of epithelial cell proliferation / regulation of protein localization / glucose homeostasis / apical part of cell / response to estradiol / heparin binding / regulation of cell population proliferation / midbody / in utero embryonic development / response to xenobiotic stimulus / negative regulation of cell population proliferation / negative regulation of DNA-templated transcription / positive regulation of DNA-templated transcription / protein-containing complex binding / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / Golgi apparatus / signal transduction / zinc ion binding / extracellular region / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||||||||||||||
Authors | Zhang, Y. / Bulkley, D. / Xin, Y. / Roberts, K.J. / Asarnow, D.E. / Sharma, A. / Myers, B.R. / Cho, W. / Cheng, Y. / Beachy, P.A. | ||||||||||||||||||
Funding support | United States, 5items
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Citation | Journal: Cell / Year: 2018 Title: Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched. Authors: Yunxiao Zhang / David P Bulkley / Yao Xin / Kelsey J Roberts / Daniel E Asarnow / Ashutosh Sharma / Benjamin R Myers / Wonhwa Cho / Yifan Cheng / Philip A Beachy / Abstract: Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity ...Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity of the 7-transmembrane protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. A central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Cholesterol activity in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability. | ||||||||||||||||||
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 | 6mg8.cif.gz | 181.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6mg8.ent.gz | 137 KB | Display | PDB format |
PDBx/mmJSON format | 6mg8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6mg8_validation.pdf.gz | 999.7 KB | Display | wwPDB validaton report |
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Full document | 6mg8_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 6mg8_validation.xml.gz | 44.8 KB | Display | |
Data in CIF | 6mg8_validation.cif.gz | 64.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mg/6mg8 ftp://data.pdbj.org/pub/pdb/validation_reports/mg/6mg8 | HTTPS FTP |
-Related structure data
Related structure data | 9111MC 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: 145357.844 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Ptch1, Ptch / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q61115 | ||
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#2: Chemical | ChemComp-CLR / Nonpolymer details | THE AUTHORS STATE THAT THE EXACT IDENTITY OF THE LIGAND IS UNKNOWN. CHOLESTEROL WAS MODELED INTO ...THE AUTHORS STATE THAT THE EXACT IDENTITY OF THE LIGAND IS UNKNOWN. CHOLESTERO | |
-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: Patched1 protein solubilized in amphipol / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.1452 MDa / Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK293 / Plasmid: BacMam |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 0.3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 23 K |
-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 FIELD / Cs: 2.7 mm |
Image recording | Average exposure time: 8 sec. / Electron dose: 38 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 5236 |
Image scans | Movie frames/image: 40 |
-Processing
Software | Name: PHENIX / Version: dev_2608: / 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: 378828 Details: Number of particles selected after rough initial 2D classification | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 245725 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||||||
Refinement | Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 91.48 Å2 | ||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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