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Yorodumi- EMDB-4939: Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-4939 | |||||||||
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Title | Structure of PTCH1 bound to a modified Hedgehog ligand ShhN-C24II: focused refinement of the membrane domain | |||||||||
Map data | Focused refinement of the membrane domain of PTCH1 | |||||||||
Sample |
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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 / prostate gland development / Activation of SMO / 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 epithelial cell differentiation / mammary gland duct morphogenesis / cell fate determination / commissural neuron axon guidance / metanephric collecting duct development / regulation of smoothened signaling pathway / dorsal/ventral pattern formation / Class B/2 (Secretin family receptors) / embryonic limb morphogenesis / ciliary membrane / negative regulation of multicellular organism growth / smoothened signaling pathway / branching involved in ureteric bud morphogenesis / cholesterol binding / positive regulation of epidermal cell differentiation / dendritic growth cone / keratinocyte proliferation / spermatid development / positive regulation of cholesterol efflux / negative regulation of keratinocyte proliferation / negative regulation of osteoblast differentiation / embryonic organ development / Hedgehog 'off' state / axonal growth cone / negative regulation of smoothened signaling pathway / heart morphogenesis / response to mechanical stimulus / response to retinoic acid / negative regulation of stem cell proliferation / regulation of mitotic cell cycle / cyclin binding / stem cell proliferation / caveola / 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 / protein processing / regulation of protein localization / endocytic vesicle membrane / apical part of cell / response to estradiol / glucose homeostasis / heparin binding / midbody / in utero embryonic development / response to xenobiotic stimulus / intracellular membrane-bounded organelle / protein-containing complex binding / positive regulation of DNA-templated transcription / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Korkhov VM / Qi C | |||||||||
Funding support | Switzerland, 1 items
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Citation | Journal: Sci Adv / Year: 2019 Title: Structural basis of sterol recognition by human hedgehog receptor PTCH1. Authors: Chao Qi / Giulio Di Minin / Irene Vercellino / Anton Wutz / Volodymyr M Korkhov / Abstract: Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog ...Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4-Å cryo-EM structure of the human PTCH1 bound to ShhN, a modified hedgehog ligand mimicking its palmitoylated form. The membrane-embedded part of PTCH1 is surrounded by 10 sterol molecules at the inner and outer lipid bilayer portion of the protein. The annular sterols interact at multiple sites with both the sterol-sensing domain (SSD) and the SSD-like domain (SSDL), which are located on opposite sides of PTCH1. The structure reveals a possible route for sterol translocation across the lipid bilayer by PTCH1 and homologous transporters. | |||||||||
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_4939.map.gz | 3.6 MB | EMDB map data format | |
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Header (meta data) | emd-4939-v30.xml emd-4939.xml | 14.7 KB 14.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_4939_fsc.xml | 10.7 KB | Display | FSC data file |
Images | emd_4939.png | 45.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-4939 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-4939 | HTTPS FTP |
-Validation report
Summary document | emd_4939_validation.pdf.gz | 236 KB | Display | EMDB validaton report |
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Full document | emd_4939_full_validation.pdf.gz | 235.1 KB | Display | |
Data in XML | emd_4939_validation.xml.gz | 11.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4939 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-4939 | HTTPS FTP |
-Related 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_4939.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Focused refinement of the membrane domain of PTCH1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.8141 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II
Entire | Name: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II |
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Components |
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-Supramolecule #1: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II
Supramolecule | Name: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II
Supramolecule | Name: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-Supramolecule #3: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II
Supramolecule | Name: Complex of PTCH1 with a modified Hedgehog ligand ShhN-C24II type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
-Macromolecule #1: Protein patched homolog 1
Macromolecule | Name: Protein patched homolog 1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFKL GCYIQKNCGK FLVVGLLIFG AFAVGLKAAN LETNVEELWV EVGGRVSREL NYTRQKIGEE AMFNPQLMIQ TPKEEGANVL ...String: MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFKL GCYIQKNCGK FLVVGLLIFG AFAVGLKAAN LETNVEELWV EVGGRVSREL NYTRQKIGEE AMFNPQLMIQ TPKEEGANVL TTEALLQHLD SALQASRVHV YMYNRQWKLE HLCYKSGELI TETGYMDQII EYLYPCLIIT PLDCFWEGAK LQSGTAYLLG KPPLRWTNFD PLEFLEELKK INYQVDSWEE MLNKAEVGHG YMDRPCLNPA DPDCPATAPN KNSTKPLDMA LVLNGGCHGL SRKYMHWQEE LIVGGTVKNS TGKLVSAHAL QTMFQLMTPK QMYEHFKGYE YVSHINWNED KAAAILEAWQ RTYVEVVHQS VAQNSTQKVL SFTTTTLDDI LKSFSDVSVI RVASGYLLML AYACLTMLRW DCSKSQGAVG LAGVLLVALS VAAGLGLCSL IGISFNAATT QVLPFLALGV GVDDVFLLAH AFSETGQNKR IPFEDRTGEC LKRTGASVAL TSISNVTAFF MAALIPIPAL RAFSLQAAVV VVFNFAMVLL IFPAILSMDL YRREDRRLDI FCCFTSPCVS RVIQVEPQAY TDTHDNTRYS PPPPASSHSF AHETQITMQS TVQLRTEYDP HTHVYYTTAE PRSEISVQPV TVTQDTLSCQ SPESTSSTRD LLSQFSDSSL HCLEPPCTKW TLSSFAEKHY APFLLKPKAK VVVIFLFLGL LGVSLYGTTR VRDGLDLTDI VPRETREYDF IAAQFKYFSF YNMYIVTQKA DYPNIQHLLY DLHRSFSNVK YVMLEENKQL PKMWLHYFRD WLQGLQDAFD SDWETGKIMP NNYKNGSDDG VLAYKLLVQT GSRDKPIDIS QLTKQRLVDA DGIINPSAFY IYLTAWVSND PVAYAASQAN IRPHRPEWVH DKADYMPETR LRIPAAEPIE YAQFPFYLNG LRDTSDFVEA IEKVRTICSN YTSLGLSSYP NGYPFLFWEQ YIGLRHWLLL FISVVLACTF LVCAVFLLNP WTAGIIVMVL ALMTVELFGM MGLIGIKLSA VPVVILIASV GIGVEFTVHV ALAFLTAIGD KNRRAVLALE HMFAPVLDGA VSTLLGVLML AGSEFDFIVR YFFAVLAILT ILGVLNGLVL LPVLLSFFGP YPEVSPANAA ALEVLFQGPG GVSKGEELFT GVVPILVELD GDVNGHKFSV SGEGEGDATY GKLTLKFICT TGKLPVPWPT LVTTFGYGLQ CFARYPDHMK QHDFFKSAMP EGYVQERTIF FKDDGNYKTR AEVKFEGDTL VNRIELKGID FKEDGNILGH KLEYNYNSHN VYIMADKQKN GIKVNFKIRH NIEDGSVQLA DHYQQNTPIG DGPVLLPDNH YLSYQSALSK DPNEKRDHMV LLEFVTAAGI TLGMDELYKA ASAWSHPQFE KGGGSGGGSG GSAWSHPQFE K |
-Macromolecule #2: Sonic hedgehog protein
Macromolecule | Name: Sonic hedgehog protein / type: protein_or_peptide / ID: 2 / Details: ShhN-C24II, a modified sonic hedgehog protein / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Escherichia coli BL21 (bacteria) |
Sequence | String: MKKHHHHHHG SGMSDSEVNQ EAKPEVKPEV KPETHINLKV SDGSSEIFFK IKKTTPLRRL MEAFAKRQGK EMDSLRFLYD GIRIQADQTP EDLDMEDNDI IEAHREQIGG IIGPGRGFGK RRHPKKLTPL AYKQFIPNVA EKTLGASGRY EGKISRNSER FKELTPNYNP ...String: MKKHHHHHHG SGMSDSEVNQ EAKPEVKPEV KPETHINLKV SDGSSEIFFK IKKTTPLRRL MEAFAKRQGK EMDSLRFLYD GIRIQADQTP EDLDMEDNDI IEAHREQIGG IIGPGRGFGK RRHPKKLTPL AYKQFIPNVA EKTLGASGRY EGKISRNSER FKELTPNYNP DIIFKDEENT GADRLMTQRC KDKLNALAIS VMNQWPGVKL RVTEGWDEDG HHSEESLHYE GRAVDITTSD RDRSKYGMLA RLAVEAGFDW VYYESKAHIH CSVKAENSVA AKSGG |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 44.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: -2.4 µm / Nominal defocus min: -0.8 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |