+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22144 | |||||||||
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Title | Structure of Human Dispatched-1 (DISP1) | |||||||||
Map data | Structure of Human Dispatched-1 (DISP1) | |||||||||
Sample |
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Function / homology | Function and homology information patched ligand maturation / diaphragm development / embryonic pattern specification / dorsal/ventral pattern formation / peptide transmembrane transporter activity / determination of left/right symmetry / peptide transport / smoothened signaling pathway / regulation of protein secretion / protein homotrimerization ...patched ligand maturation / diaphragm development / embryonic pattern specification / dorsal/ventral pattern formation / peptide transmembrane transporter activity / determination of left/right symmetry / peptide transport / smoothened signaling pathway / regulation of protein secretion / protein homotrimerization / basolateral plasma membrane / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.53 Å | |||||||||
Authors | Chen H / Liu Y / Li X | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Life Sci Alliance / Year: 2020 Title: Structure of human Dispatched-1 provides insights into Hedgehog ligand biogenesis. Authors: Hongwen Chen / Yang Liu / Xiaochun Li / Abstract: Hedgehog (HH) signaling is essential for metazoan development. The HH ligand is secreted into the extracellular space by a cell surface protein named Dispatched-1 (DISP1). Here, we report the cryo-EM ...Hedgehog (HH) signaling is essential for metazoan development. The HH ligand is secreted into the extracellular space by a cell surface protein named Dispatched-1 (DISP1). Here, we report the cryo-EM structure of human DISP1 protein. DISP1 contains 12 transmembrane helices (TMs) and two extracellular domains (ECDs). Its ECDs reveal an open state, in contrast to its structural homologues PTCH1 and NPC1, whose extracellular/luminal domains adopt a closed state. The low-resolution structure of the DISP1 complex with dual lipid-modified HH ligand reveals how the ECDs of DISP1 engage with HH ligand. Moreover, several cholesterol-like molecules are found in the TMs, implying a transport-like function of DISP1. | |||||||||
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_22144.map.gz | 59.4 MB | EMDB map data format | |
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Header (meta data) | emd-22144-v30.xml emd-22144.xml | 13 KB 13 KB | Display Display | EMDB header |
Images | emd_22144.png | 57.9 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22144 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22144 | HTTPS FTP |
-Validation report
Summary document | emd_22144_validation.pdf.gz | 451.2 KB | Display | EMDB validaton report |
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Full document | emd_22144_full_validation.pdf.gz | 450.7 KB | Display | |
Data in XML | emd_22144_validation.xml.gz | 6 KB | Display | |
Data in CIF | emd_22144_validation.cif.gz | 6.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22144 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22144 | HTTPS FTP |
-Related structure data
Related structure data | 6xe6MC 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_22144.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Structure of Human Dispatched-1 (DISP1) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.833 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 : Human dispatched-1 in complex with dual-lipidated SHH-N
Entire | Name: Human dispatched-1 in complex with dual-lipidated SHH-N |
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Components |
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-Supramolecule #1: Human dispatched-1 in complex with dual-lipidated SHH-N
Supramolecule | Name: Human dispatched-1 in complex with dual-lipidated SHH-N type: organelle_or_cellular_component / 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: HEK293S GnTI- / Recombinant plasmid: pEG BacMam |
-Macromolecule #1: Protein dispatched homolog 1
Macromolecule | Name: Protein dispatched homolog 1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 124.49875 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAWSHPQFEK SRPFKLPKSY AALIADWPVV VLGMCTMFIV VCALVGVLVP ELPDFSDPLL GFEPRGTAIG QRLVTWNNMV KNTGYKATL ANYPFKYADE QAKSHRDDRW SDDHYEREKR EVDWNFHKDS FFCDVPSDRY SRVVFTSSGG ETLWNLPAIK S MCNVDNSR ...String: MAWSHPQFEK SRPFKLPKSY AALIADWPVV VLGMCTMFIV VCALVGVLVP ELPDFSDPLL GFEPRGTAIG QRLVTWNNMV KNTGYKATL ANYPFKYADE QAKSHRDDRW SDDHYEREKR EVDWNFHKDS FFCDVPSDRY SRVVFTSSGG ETLWNLPAIK S MCNVDNSR IRSHPQFGDL CQRTTAASCC PSWTLGNYIA ILNNRSSCQK IVERDVSHTL KLLRTCAKHY QNGTLGPDCW DM AARRKDQ LKCTNVPRKC TKYNAVYQIL HYLVDKDFMT PKTADYATPA LKYSMLFSPT EKGESMMNIY LDNFENWNSS DGV TTITGI EFGIKHSLFQ DYLLMDTVYP AIAIVIVLLV MCVYTKSMFI TLMTMFAIIS SLIVSYFLYR VVFHFEFFPF MNLT ALIIL VGIGADDAFV LCDVWNYTKF DKPHAETSET VSITLQHAAL SMFVTSFTTA AAFYANYVSN ITAIRCFGVY AGTAI LVNY VLMVTWLPAV VVLHERYLLN IFTCFKKPQQ QIYDNKSCWT VACQKCHKVL FAISEASRIF FEKVLPCIVI KFRYLW LFW FLALTVGGAY IVCINPKMKL PSLELSEFQV FRSSHPFERY DAEYKKLFMF ERVHHGEELH MPITVIWGVS PEDNGNP LN PKSKGKLTLD SSFNIASPAS QAWILHFCQK LRNQTFFYQT DEQDFTSCFI ETFKQWMENQ DCDEPALYPC CSHWSFPY K QEIFELCIKR AIMELERSTG YHLDSKTPGP RFDINDTIRA VVLEFQSTYL FTLAYEKMHQ FYKEVDSWIS SELSSAPEG LSNGWFVSNL EFYDLQDSLS DGTLIAMGLS VAVAFSVMLL TTWNIIISLY AIISIAGTIF VTVGSLVLLG WELNVLESVT ISVAVGLSV DFAVHYGVAY RLAPDPDREG KVIFSLSRVG SAMAMAALTT FVAGAMMMPS TVLAYTQLGT FMMLIMCISW A FATFFFQC MCRCLGPQGT CGQIPLPKKL QCSAFSHALS TSPSDKGQSK THTINAYHLD PRGPKSELEH EFYELEPLAS HS CTAPEKT TYEETHICSE FFNSQAKNLG MPVHAAYNSE LSKSTESDAG SDYKDDDDK |
-Macromolecule #2: CHOLESTEROL HEMISUCCINATE
Macromolecule | Name: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 2 / Number of copies: 5 / Formula: Y01 |
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Molecular weight | Theoretical: 486.726 Da |
Chemical component information | ChemComp-Y01: |
-Macromolecule #3: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 3 / Number of copies: 1 / 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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 6 mg/mL | |||||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber temperature: 293 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 62.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Number classes used: 2 / Resolution.type: BY AUTHOR / Resolution: 4.53 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 400432 |
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Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |
Final 3D classification | Software - Name: RELION |