|Entry||Database: PDB / ID: 6dmy|
|Title||Cryo-EM structure of human Ptch1 and ShhN complex|
|Keywords||PROTEIN BINDING / Receptor / RND family|
|Function / homology||Intein N-terminal splicing motif profile. / Hh mutants that don't undergo autocatalytic processing are degraded by ERAD / Release of Hh-Np from the secreting cell / Hedgehog 'off' state / Ligand-receptor interactions / Hedgehog 'on' state / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Hedgehog ligand biogenesis / Class B/2 (Secretin family receptors) ...Intein N-terminal splicing motif profile. / Hh mutants that don't undergo autocatalytic processing are degraded by ERAD / Release of Hh-Np from the secreting cell / Hedgehog 'off' state / Ligand-receptor interactions / Hedgehog 'on' state / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Hedgehog ligand biogenesis / Class B/2 (Secretin family receptors) / Hedgehog, N-terminal signalling domain / Sterol-sensing domain / Hedgehog protein / Hedgehog protein, Hint domain / Protein patched/dispatched / Hint domain C-terminal / Hint domain N-terminal / Transmembrane receptor, patched / Intein N-terminal splicing region / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / Hint domain superfamily / Hint module / Hedgehog amino-terminal signalling domain / Patched family / Sterol-sensing domain (SSD) profile. / regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry / response to chlorate / neural plate axis specification / hedgehog receptor activity / cell proliferation involved in metanephros development / cell differentiation involved in kidney development / smoothened signaling pathway involved in dorsal/ventral neural tube patterning / neural tube patterning / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of ureter smooth muscle cell differentiation / right lung development / epithelial-mesenchymal signaling involved in prostate gland development / negative regulation of ureter smooth muscle cell differentiation / regulation of mesenchymal cell proliferation involved in prostate gland development / left lung development / negative regulation of kidney smooth muscle cell differentiation / tracheoesophageal septum formation / positive regulation of kidney smooth muscle cell differentiation / positive regulation of sclerotome development / positive regulation of skeletal muscle cell proliferation / primary prostatic bud elongation / positive regulation of mesenchymal cell proliferation involved in ureter development / smoothened binding / regulation of odontogenesis / regulation of prostatic bud formation / spinal cord dorsal/ventral patterning / hindgut morphogenesis / polarity specification of anterior/posterior axis / morphogen activity / epidermal cell fate specification / cerebellar granule cell precursor proliferation / bud outgrowth involved in lung branching / striated muscle tissue development / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / hedgehog family protein binding / positive regulation of immature T cell proliferation in thymus / metanephric mesenchymal cell proliferation involved in metanephros development / determination of left/right asymmetry in lateral mesoderm / negative regulation of alpha-beta T cell differentiation / positive regulation of striated muscle cell differentiation / ventral midline development / positive regulation of hh target transcription factor activity / artery development / lung epithelium development / formation of anatomical boundary / smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation / hindlimb morphogenesis / trachea morphogenesis / telencephalon regionalization / spinal cord motor neuron differentiation / laminin-1 binding / negative regulation of mesenchymal cell apoptotic process / myotube differentiation / salivary gland cavitation / stem cell development / intermediate filament organization / mammary gland duct morphogenesis / pattern specification process / positive regulation of T cell differentiation in thymus / hindbrain development / dorsal/ventral neural tube patterning / negative regulation of cholesterol efflux / patched binding / neuroblast proliferation / lymphoid progenitor cell differentiation / limb morphogenesis / somite development / embryonic foregut morphogenesis / negative regulation of multicellular organism growth / negative regulation of cell division / cellular response to cholesterol / negative regulation of smoothened signaling pathway / positive regulation of cholesterol efflux / renal system development / mesenchymal cell proliferation involved in lung development|
Function and homology information
|Specimen source||Homo sapiens (human)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 3.6 Å resolution|
|Authors||Yan, N. / Gong, X. / Qian, H.W.|
|Citation||Journal: Science / Year: 2018|
Title: Structural basis for the recognition of Sonic Hedgehog by human Patched1.
Authors: Xin Gong / Hongwu Qian / Pingping Cao / Xin Zhao / Qiang Zhou / Jianlin Lei / Nieng Yan
Abstract: The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the structures of human Ptch1 ...The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms, respectively, as determined by cryo-electron microscopy. Ptch1 comprises two interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments (TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2 and the other in the membrane-facing cavity of the SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding-deficient Ptch1 mutant displays pronounced conformational rearrangements.
SummaryFull reportAbout validation report
|Date||Deposition: Jun 5, 2018 / Release: Jul 11, 2018|
|Structure viewer||Molecule: |
Downloads & links
A: Protein patched homolog 1
B: Sonic hedgehog protein
-Protein/peptide , 2 types, 2 molecules A
|#1: Protein/peptide|| |
Mass: 150189.578 Da / Num. of mol.: 1 / Source: (gene. exp.) Homo sapiens (human) / Gene: PTCH1, PTCH / Production host: Homo sapiens (human) / References: UniProt: Q13635
|#2: Protein/peptide|| |
Mass: 19934.461 Da / Num. of mol.: 1 / Source: (gene. exp.) Homo sapiens (human) / Gene: SHH
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: Q15465
-Non-polymers , 5 types, 13 molecules
|#4: Chemical||#5: Chemical|| ChemComp-SER / ||#6: Chemical|| ChemComp-ZN / ||#7: Chemical|
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: Patch1 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: 1 / Source: RECOMBINANT|
|Source (natural)||Organism: Homo sapiens (human)|
|Source (recombinant)||Organism: Homo sapiens (human)|
|Buffer solution||pH: 8|
|Specimen||Conc.: 15 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Vitrification||Cryogen name: ETHANE|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Microscope model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|Software||Name: PHENIX / Version: 1.11rc3_2542: / Classification: refinement|
|CTF correction||Type: NONE|
|3D reconstruction||Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 137823 / Symmetry type: POINT|
|Refine LS restraints|
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