|Entry||Database: PDB / ID: 6dmy|
|Title||Cryo-EM structure of human Ptch1 and ShhN complex|
|Keywords||PROTEIN BINDING / Receptor / RND family|
|Function / homology||Sterol-sensing domain (SSD) profile. / Hedgehog protein / Hedgehog 'off' state / Ligand-receptor interactions / Release of Hh-Np from the secreting cell / Hedgehog 'on' state / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Class B/2 (Secretin family receptors) / Hedgehog ligand biogenesis ...Sterol-sensing domain (SSD) profile. / Hedgehog protein / Hedgehog 'off' state / Ligand-receptor interactions / Release of Hh-Np from the secreting cell / Hedgehog 'on' state / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Class B/2 (Secretin family receptors) / Hedgehog ligand biogenesis / Hedgehog, N-terminal signalling domain / Intein N-terminal splicing motif profile. / Sterol-sensing domain / 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 / Hh mutants that don't undergo autocatalytic processing are degraded by ERAD / regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry / response to chlorate / hedgehog receptor activity / neural plate axis specification / cell proliferation involved in metanephros development / smoothened signaling pathway involved in dorsal/ventral neural tube patterning / cell differentiation involved in kidney development / neural tube patterning / left lung development / regulation of mesenchymal cell proliferation involved in prostate gland development / right lung development / negative regulation of kidney smooth muscle cell differentiation / primary prostatic bud elongation / epithelial-mesenchymal signaling involved in prostate gland development / positive regulation of ureter smooth muscle cell differentiation / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of skeletal muscle cell proliferation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of sclerotome development / tracheoesophageal septum formation / positive regulation of kidney smooth muscle cell differentiation / regulation of odontogenesis / regulation of prostatic bud formation / smoothened binding / positive regulation of mesenchymal cell proliferation involved in ureter development / spinal cord dorsal/ventral patterning / hindgut morphogenesis / polarity specification of anterior/posterior axis / striated muscle tissue development / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / cerebellar granule cell precursor proliferation / epidermal cell fate specification / bud outgrowth involved in lung branching / morphogen activity / hedgehog family protein binding / positive regulation of immature T cell proliferation in thymus / metanephric mesenchymal cell proliferation involved in metanephros development / positive regulation of striated muscle cell differentiation / negative regulation of alpha-beta T cell differentiation / determination of left/right asymmetry in lateral mesoderm / 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 / salivary gland cavitation / myotube differentiation / stem cell development / intermediate filament organization / mammary gland duct morphogenesis / pattern specification process / positive regulation of T cell differentiation in thymus / dorsal/ventral neural tube patterning / negative regulation of cholesterol efflux / patched binding / neuroblast proliferation / lymphoid progenitor cell differentiation / limb morphogenesis / somite development / negative regulation of multicellular organism growth / negative regulation of cell division / cellular response to cholesterol / negative regulation of smoothened signaling pathway / renal system development / embryonic skeletal system development / embryonic foregut morphogenesis / embryonic digestive tract morphogenesis / limb bud formation|
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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