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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24467 | |||||||||
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Title | Cryo-EM structure of Xenopus Patched-1 in nanodisc | |||||||||
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Function / homology | hedgehog receptor activity / Transmembrane receptor, patched / Sterol-sensing domain of SREBP cleavage-activation / Protein patched/dispatched / Patched family / Sterol-sensing domain (SSD) profile. / Sterol-sensing domain / membrane => GO:0016020 / Patched-1![]() | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Huang P / Lian T / Jiang J / Salic A | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex. Authors: Pengxiang Huang / Bradley M Wierbowski / Tengfei Lian / Charlene Chan / Sara García-Linares / Jiansen Jiang / Adrian Salic / ![]() Abstract: The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and ...The dually lipidated Sonic hedgehog (SHH) morphogen signals through the tumor suppressor membrane protein Patched1 (PTCH1) to activate the Hedgehog pathway, which is fundamental in development and cancer. SHH engagement with PTCH1 requires the GAS1 coreceptor, but the mechanism is unknown. We demonstrate a unique role for GAS1, catalyzing SHH-PTCH1 complex assembly in vertebrate cells by direct SHH transfer from the extracellular SCUBE2 carrier to PTCH1. Structure of the GAS1-SHH-PTCH1 transition state identifies how GAS1 recognizes the SHH palmitate and cholesterol modifications in modular fashion and how it facilitates lipid-dependent SHH handoff to PTCH1. Structure-guided experiments elucidate SHH movement from SCUBE2 to PTCH1, explain disease mutations, and demonstrate that SHH-induced PTCH1 dimerization causes its internalization from the cell surface. These results define how the signaling-competent SHH-PTCH1 complex assembles, the key step triggering the Hedgehog pathway, and provide a paradigm for understanding morphogen reception and its regulation. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 2.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.7 KB 10.7 KB | Display Display | ![]() |
Images | ![]() | 144.8 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 322.1 KB | Display | ![]() |
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Full document | ![]() | 321.7 KB | Display | |
Data in XML | ![]() | 6.1 KB | Display | |
Data in CIF | ![]() | 7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7rhrMC ![]() 7rhqC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : patched
Entire | Name: patched |
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Components |
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-Supramolecule #1: patched
Supramolecule | Name: patched / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Patched-1
Macromolecule | Name: Patched-1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 134.622391 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASAACAAEL GASGEAAAQP RVVRRRGRSR RVAPPDHDYL QRPSYCDANF ALQQISEGKA IGRKAPLWLR AFFQRQLFKL GCYIQKNCG KFLVVGLLIF GAFAVGLRAA NLETNVEELW VEVGGRVSRE LDYTRQKIGE EAMFNPQLMI QTPLEDGANV L TTEALLQH ...String: MASAACAAEL GASGEAAAQP RVVRRRGRSR RVAPPDHDYL QRPSYCDANF ALQQISEGKA IGRKAPLWLR AFFQRQLFKL GCYIQKNCG KFLVVGLLIF GAFAVGLRAA NLETNVEELW VEVGGRVSRE LDYTRQKIGE EAMFNPQLMI QTPLEDGANV L TTEALLQH LHSALEATKV QVYMYNKPWK LEELCFKSGE LITEAVYVSQ IIDSMYPCLI ITPLDCFWEG AKLQSGMAYL PG KDILQWT NFDPLELLEE LKKGKLHIDI WEEMINKAEV GHGYMDRPCL NPSDKNCPYT APNKNSTKPV DVSLILSGGC YGL SKKYMH WQEELIIGGT VKNASGQIVS ALALQTMFQL MTPKQMYEHF KGHEVVSHMN WNEDKAAAIL EAWQRTYVQV VHQS VPQNS SQKVLPFTTT TLDDILKSFS DVSVIRVASG YLLMLAYACL TMLRWDCAKS QGAVGLAGVL LVALSVAAGL GLCSL IGIS FNAATTQVLP FLALGVGVDD VFLLAHAFSE TGQNKRIPFE DRTGECLKRT GASVALTSIS NVTAFFMAAL IPIPAL RAF SLQAAVVVVF NFAMVLLIFP AILSMDLYRR EVRRLDIFCC FSSPCVSRVI QIEPQAYTDN NDNTRYSLPP TYSSHSF AH ETQITMQSTV QLRTEYDPRT QLYYTTAQPR SEISVQPAAS TPQDVSGQTP ESTSSTRDLI SQFSVHGGSM QCTPDSKW T LSSFAEKHYA PFLLKPKTKV AVILGFLALL SVSLYGTTRV RDGLDLTDIV PRETREYDFI ATQFKYFSFY HMYVVTQKA DYPRAQRLLY ELHKSFVGVR YVLLEGNKQL PKMWLHYFRD WLQGLQDTFD HEWEAGKITR NDYRNASDDA VLAYKLLIQT GNSDKPINL NQLTKQRLVD ADGIIQPNAF YIYLTAWVSN DPVAYAASQA NIRPHPPEWL HDKADDRPET RTIRAAEPIE Y VQFPFYLN GLRETSDFVE AIEKVRAICN NYTSLGVSSY PNGYPFLFWE QYISLRHWLL LSISVVLACT FLVCALFLLN PW TAGIIVM VLALMTVELF GMMGLIGIKL SAVPVVILIA SVGIGVEFTV HVALAFLTAV GDKNRRAVLA LEHMFAPVLD GAV STLLGV LMLAGSEFDF IVRYFFAVLA ILTLLGVLNG LVLLPVLLSF FGPYPEVSPT NGSSSPAAAH HHHHHHHEDQ VDPR LIDGK |
-Macromolecule #3: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 3 / Number of copies: 3 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 2 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 71.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 106749 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |