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- EMDB-7796: Structure of human Patched1 in complex with native Sonic Hedgehog -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-7796 | |||||||||
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Title | Structure of human Patched1 in complex with native Sonic Hedgehog | |||||||||
![]() | A protein structure | |||||||||
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Function / homology | ![]() positive regulation of skeletal muscle cell proliferation / neural plate axis specification / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation ...positive regulation of skeletal muscle cell proliferation / neural plate axis specification / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of kidney smooth muscle cell differentiation / morphogen activity / regulation of odontogenesis / cell differentiation involved in kidney development / positive regulation of mesenchymal cell proliferation involved in ureter development / polarity specification of anterior/posterior axis / trunk neural crest cell migration / hedgehog receptor activity / response to chlorate / neural tube patterning / Formation of lateral plate mesoderm / cell proliferation involved in metanephros development / hindgut morphogenesis / striated muscle tissue development / negative regulation of alpha-beta T cell differentiation / regulation of glial cell proliferation / regulation of prostatic bud formation / metanephric mesenchymal cell proliferation involved in metanephros development / smoothened binding / formation of anatomical boundary / lung epithelium development / positive regulation of striated muscle cell differentiation / ventral midline development / hedgehog family protein binding / trachea morphogenesis / cholesterol-protein transferase activity / bud outgrowth involved in lung branching / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / epithelial-mesenchymal cell signaling / laminin-1 binding / Ligand-receptor interactions / hindlimb morphogenesis / negative regulation of cholesterol efflux / salivary gland cavitation / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / negative regulation of mesenchymal cell apoptotic process / cell development / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / epidermal cell fate specification / spinal cord motor neuron differentiation / positive regulation of T cell differentiation in thymus / cerebellar granule cell precursor proliferation / intermediate filament organization / mesenchymal cell apoptotic process / prostate gland development / embryonic skeletal system development / limb bud formation / lung lobe morphogenesis / Activation of SMO / establishment of epithelial cell polarity / skeletal muscle fiber differentiation / limb morphogenesis / thalamus development / embryonic digestive tract morphogenesis / somite development / patched binding / embryonic foregut morphogenesis / negative regulation of cell division / epithelial cell proliferation involved in salivary gland morphogenesis / hindbrain development / animal organ formation / ectoderm development / positive regulation of skeletal muscle tissue development / neuron fate commitment / stem cell development / cellular response to cholesterol / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / skeletal muscle cell proliferation / negative thymic T cell selection / lymphoid progenitor cell differentiation / positive regulation of immature T cell proliferation in thymus / dorsal/ventral neural tube patterning / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / smooth muscle tissue development / regulation of stem cell proliferation / oligodendrocyte development / male genitalia development / artery development / positive regulation of astrocyte differentiation / pattern specification process / self proteolysis / pharyngeal system development / epithelial cell proliferation involved in prostate gland development / mammary gland epithelial cell differentiation Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / Resolution: 3.5 Å | |||||||||
![]() | Qi X / Li X | |||||||||
![]() | ![]() Title: Structures of human Patched and its complex with native palmitoylated sonic hedgehog. Authors: Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Jiawei Wang / Xiaochun Li / ![]() ![]() Abstract: Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms. Whereas deficient HH signalling leads to birth defects, unrestrained HH ...Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms. Whereas deficient HH signalling leads to birth defects, unrestrained HH signalling is implicated in human cancers. N-terminally palmitoylated HH releases the repression of Patched to the oncoprotein smoothened (SMO); however, the mechanism by which HH recognizes Patched is unclear. Here we report cryo-electron microscopy structures of human patched 1 (PTCH1) alone and in complex with the N-terminal domain of 'native' sonic hedgehog (native SHH-N has both a C-terminal cholesterol and an N-terminal fatty-acid modification), at resolutions of 3.5 Å and 3.8 Å, respectively. The structure of PTCH1 has internal two-fold pseudosymmetry in the transmembrane core, which features a sterol-sensing domain and two homologous extracellular domains, resembling the architecture of Niemann-Pick C1 (NPC1) protein. The palmitoylated N terminus of SHH-N inserts into a cavity between the extracellular domains of PTCH1 and dominates the PTCH1-SHH-N interface, which is distinct from that reported for SHH-N co-receptors. Our biochemical assays show that SHH-N may use another interface, one that is required for its co-receptor binding, to recruit PTCH1 in the absence of a covalently attached palmitate. Our work provides atomic insights into the recognition of the N-terminal domain of HH (HH-N) by PTCH1, offers a structural basis for cooperative binding of HH-N to various receptors and serves as a molecular framework for HH signalling and its malfunction in disease. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 12.5 KB 12.5 KB | Display Display | ![]() |
Images | ![]() | 32.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6oevMC ![]() 7795C ![]() 6oeuC ![]() 6d4j C: citing same article ( M: atomic model generated by this map |
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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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Annotation | A protein structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1 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 : Ptc
Entire | Name: Ptc |
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Components |
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-Supramolecule #1: Ptc
Supramolecule | Name: Ptc / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
Molecular weight | Experimental: 121 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: ![]() |
Molecular weight | Theoretical: 160.714406 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFK LGCYIQKNCG KFLVVGLLIF GAFAVGLKAA NLETNVEELW VEVGGRVSRE LNYTRQKIGE EAMFNPQLMI Q TPKEEGAN ...String: MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFK LGCYIQKNCG KFLVVGLLIF GAFAVGLKAA NLETNVEELW VEVGGRVSRE LNYTRQKIGE EAMFNPQLMI Q TPKEEGAN VLTTEALLQH LDSALQASRV HVYMYNRQWK LEHLCYKSGE LITETGYMDQ IIEYLYPCLI ITPLDCFWEG AK LQSGTAY LLGKPPLRWT NFDPLEFLEE LKKINYQVDS WEEMLNKAEV GHGYMDRPCL NPADPDCPAT APNKNSTKPL DMA LVLNGG CHGLSRKYMH WQEELIVGGT VKNSTGKLVS AHALQTMFQL MTPKQMYEHF KGYEYVSHIN WNEDKAAAIL EAWQ RTYVE VVHQSVAQNS TQKVLSFTTT TLDDILKSFS DVSVIRVASG YLLMLAYACL TMLRWDCSKS QGAVGLAGVL LVALS VAAG LGLCSLIGIS FNAATTQVLP FLALGVGVDD VFLLAHAFSE TGQNKRIPFE DRTGECLKRT GASVALTSIS NVTAFF MAA LIPIPALRAF SLQAAVVVVF NFAMVLLIFP AILSMDLYRR EDRRLDIFCC FTSPCVSRVI QVEPQAYTDT HDNTRYS PP PPYSSHSFAH ETQITMQSTV QLRTEYDPHT HVYYTTAEPR SEISVQPVTV TQDTLSCQSP ESTSSTRDLL SQFSDSSL H CLEPPCTKWT LSSFAEKHYA PFLLKPKAKV VVIFLFLGLL GVSLYGTTRV RDGLDLTDIV PRETREYDFI AAQFKYFSF YNMYIVTQKA DYPNIQHLLY DLHRSFSNVK YVMLEENKQL PKMWLHYFRD WLQGLQDAFD SDWETGKIMP NNYKNGSDDG VLAYKLLVQ TGSRDKPIDI SQLTKQRLVD ADGIINPSAF YIYLTAWVSN DPVAYAASQA NIRPHRPEWV HDKADYMPET R LRIPAAEP IEYAQFPFYL NGLRDTSDFV EAIEKVRTIC SNYTSLGLSS YPNGYPFLFW EQYIGLRHWL LLFISVVLAC TF LVCAVFL LNPWTAGIIV MVLALMTVEL FGMMGLIGIK LSAVPVVILI ASVGIGVEFT VHVALAFLTA IGDKNRRAVL ALE HMFAPV LDGAVSTLLG VLMLAGSEFD FIVRYFFAVL AILTILGVLN GLVLLPVLLS FFGPYPEVSP ANGLNRLPTP SPEP PPSVV RFAMPPGHTH SGSDSSDSEY SSQTTVSGLS EELRHYEAQQ GAGGPAHQVI VEATENPVFA HSTVVHPESR HHPPS NPRQ QPHLDSGSLP PGRQGQQPRR DPPREGLWPP PYRPRRDAFE ISTEGHSGPS NRARWGPRGA RSHNPRNPAS TAMGSS VPG YCQPITTVTA SASVTVAVHP PPVPGPGRNP RGGLCPGYPE TDHGLFEDPH VPFHVRCERR DSKVEVIELQ DVECEER PR GSSSN |
-Macromolecule #2: Sonic hedgehog protein
Macromolecule | Name: Sonic hedgehog protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 19.594039 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: CGPGRGFGKR RHPKKLTPLA YKQFIPNVAE KTLGASGRYE GKISRNSERF KELTPNYNPD IIFKDEENTG ADRLMTQRCK DKLNALAIS VMNQWPGVKL RVTEGWDEDG HHSEESLHYE GRAVDITTSD RDRSKYGMLA RLAVEAGFDW VYYESKAHIH C SVKAENSV AAKSGG |
-Macromolecule #3: N-ACETYL-D-GLUCOSAMINE
Macromolecule | Name: N-ACETYL-D-GLUCOSAMINE / type: ligand / ID: 3 / Number of copies: 6 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
-Macromolecule #4: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 4 / Number of copies: 1 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #5: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 5 / Number of copies: 1 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ![]() ChemComp-PLM: |
-Experimental details
-Structure determination
![]() | single particle reconstruction |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7 |
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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: 1.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: DARK FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 789118 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |