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Yorodumi- EMDB-9111: Structural basis for cholesterol transport-like activity of the H... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9111 | ||||||||||||||||||
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Title | Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched | ||||||||||||||||||
Map data | PTCH1 monomer | ||||||||||||||||||
Sample |
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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 | Homo sapiens (human) / Mus musculus (house mouse) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.6 Å | ||||||||||||||||||
Authors | Zhang Y / Bulkley D / Xin Y / Roberts KJ / Asarnow DE / Sharma A / Myers BR / Cho W / Cheng Y / Beachy PA | ||||||||||||||||||
Funding support | United States, 5 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9111.map.gz | 1.5 MB | EMDB map data format | |
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Header (meta data) | emd-9111-v30.xml emd-9111.xml | 24.1 KB 24.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_9111_fsc.xml | 10.6 KB | Display | FSC data file |
Images | emd_9111.png | 50 KB | ||
Others | emd_9111_additional_1.map.gz emd_9111_additional_2.map.gz emd_9111_half_map_1.map.gz emd_9111_half_map_2.map.gz | 2.8 MB 2.9 MB 55.5 MB 55.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9111 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9111 | HTTPS FTP |
-Validation report
Summary document | emd_9111_validation.pdf.gz | 449.1 KB | Display | EMDB validaton report |
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Full document | emd_9111_full_validation.pdf.gz | 448.7 KB | Display | |
Data in XML | emd_9111_validation.xml.gz | 18.3 KB | Display | |
Data in CIF | emd_9111_validation.cif.gz | 23.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9111 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9111 | HTTPS FTP |
-Related structure data
Related structure data | 6mg8MC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9111.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | PTCH1 monomer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.31 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: PTCH1 dimer, C2 symmetry
File | emd_9111_additional_1.map | ||||||||||||
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Annotation | PTCH1 dimer, C2 symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: PTCH1 dimer, C1 symmetry
File | emd_9111_additional_2.map | ||||||||||||
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Annotation | PTCH1 dimer, C1 symmetry | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Independent half map 2 used to calculate final monomer map
File | emd_9111_half_map_1.map | ||||||||||||
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Annotation | Independent half map 2 used to calculate final monomer map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Independent half map 1 used to calculate final monomer map
File | emd_9111_half_map_2.map | ||||||||||||
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Annotation | Independent half map 1 used to calculate final monomer map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Patched1 protein solubilized in amphipol
Entire | Name: Patched1 protein solubilized in amphipol |
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Components |
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-Supramolecule #1: Patched1 protein solubilized in amphipol
Supramolecule | Name: Patched1 protein solubilized in amphipol / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 / Recombinant plasmid: BacMam |
Molecular weight | Theoretical: 145.2 KDa |
-Macromolecule #1: Protein patched homolog 1
Macromolecule | Name: Protein patched homolog 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 145.357844 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASAGNAAGA LGRQAGGGRR RRTGGPHRAA PDRDYLHRPS YCDAAFALEQ ISKGKATGRK APLWLRAKFQ RLLFKLGCYI QKNCGKFLV VGLLIFGAFA VGLKAANLET NVEELWVEVG GRVSRELNYT RQKIGEEAMF NPQLMIQTPK EEGANVLTTE A LLQHLDSA ...String: MASAGNAAGA LGRQAGGGRR RRTGGPHRAA PDRDYLHRPS YCDAAFALEQ ISKGKATGRK APLWLRAKFQ RLLFKLGCYI QKNCGKFLV VGLLIFGAFA VGLKAANLET NVEELWVEVG GRVSRELNYT RQKIGEEAMF NPQLMIQTPK EEGANVLTTE A LLQHLDSA LQASRVHVYM YNRQWKLEHL CYKSGELITE TGYMDQIIEY LYPCLIITPL DCFWEGAKLQ SGTAYLLGKP PL RWTNFDP LEFLEELKKI NYQVDSWEEM LNKAEVGHGY MDRPCLNPAD PDCPATAPNK NSTKPLDVAL VLNGGCQGLS RKY MHWQEE LIVGGTVKNA TGKLVSAHAL QTMFQLMTPK QMYEHFRGYD YVSHINWNED RAAAILEAWQ RTYVEVVHQS VAPN STQKV LPFTTTTLDD ILKSFSDVSV IRVASGYLLM LAYACLTMLR WDCSKSQGAV GLAGVLLVAL SVAAGLGLCS LIGIS FNAA TTQVLPFLAL GVGVDDVFLL AHAFSETGQN KRIPFEDRTG ECLKRTGASV ALTSISNVTA FFMAALIPIP ALRAFS LQA AVVVVFNFAM VLLIFPAILS MDLYRREDRR LDIFCCFTSP CVSRVIQVEP QAYTEPMQST VQLRTEYDPH THVYYTT AE PRSEISVQPV TVTQDNLSCQ SPESTSSTRD LLSQFSDSSL HCLEPPCTKW TLSSFAEKHY APFLLKPKAK VVVILLFL G LLGVSLYGTT RVRDGLDLTD IVPRETREYD FIAAQFKYFS FYNMYIVTQK ADYPNIQHLL YDLHKSFSNV KYVMLEENK QLPQMWLHYF RDWLQGLQDA FDSDWETGRI MPNNYKNGSD DGVLAYKLLV QTGSRDKPID ISQLTKQRLV DADGIINPSA FYIYLTAWV SNDPVAYAAS QANIRPHRPE WVHDKADYMP ETRLRIPAAE PIEYAQFPFY LNGLRDTSDF VEAIEKVRVI C NNYTSLGL SSYPNGYPFL FWEQYISLRH WLLLSISVVL ACTFLVCAVF LLNPWTAGII VMVLALMTVE LFGMMGLIGI KL SAVPVVI LIASVGIGVE FTVHVALAFL TAIGDKNHRA MLALEHMFAP VLDGAVSTLL GVLMLAGSEF DFIVRYFFAV LAI LTVLGV LNGLVLLPVL LSFFGPCPEV SPANGLNRLP TPSPEPPPSV VRFAVPPGHT NNGSDSSDSE YSSQTTVSGI SEEL RQYEA QQGAGGPAHQ VIVEATENPV FARSTVVHPD SRHQPPLTPR QQPHLDSGSL SPGRQGQQPR RDMDEKTTGW RGGHV VEGL AGELEQLRAR LEHHPQGQRE P |
-Macromolecule #2: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 2 / Number of copies: 4 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.3 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: AIR |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 23 K / Instrument: FEI VITROBOT MARK III |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number grids imaged: 1 / Number real images: 5236 / Average exposure time: 8.0 sec. / Average electron dose: 38.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL |
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Output model | PDB-6mg8: |