|Entry||Database: PDB / ID: 6dmy|
|Title||Cryo-EM structure of human Ptch1 and ShhN complex|
|Keywords||PROTEIN BINDING / Receptor / RND family|
|Function / homology||Patched family / Sterol-sensing domain / Hh mutants that don't undergo autocatalytic processing are degraded by ERAD / Hedgehog ligand biogenesis / Hedgehog 'off' state / Ligand-receptor interactions / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Intein N-terminal splicing motif profile. / Class B/2 (Secretin family receptors) ...Patched family / Sterol-sensing domain / Hh mutants that don't undergo autocatalytic processing are degraded by ERAD / Hedgehog ligand biogenesis / Hedgehog 'off' state / Ligand-receptor interactions / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Intein N-terminal splicing motif profile. / Class B/2 (Secretin family receptors) / Hedgehog, N-terminal signalling domain / Sterol-sensing domain (SSD) profile. / Hedgehog 'on' state / Release of Hh-Np from the secreting cell / Transmembrane receptor, patched / Hedgehog amino-terminal signalling domain / Hedgehog protein / Hint domain superfamily / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / Intein N-terminal splicing region / Hint module / Hint domain N-terminal / Hint domain C-terminal / Protein patched/dispatched / Hedgehog protein, Hint domain / regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry / neural plate axis specification / cell proliferation involved in metanephros development / hedgehog receptor activity / cell differentiation involved in kidney development / smoothened signaling pathway involved in dorsal/ventral neural tube patterning / response to chlorate / positive regulation of sclerotome development / regulation of mesenchymal cell proliferation involved in prostate gland development / epithelial-mesenchymal signaling involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / left lung development / positive regulation of skeletal muscle cell proliferation / primary prostatic bud elongation / 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 / right lung development / neural tube patterning / regulation of odontogenesis / regulation of prostatic bud formation / positive regulation of mesenchymal cell proliferation involved in ureter development / spinal cord dorsal/ventral patterning / hindgut morphogenesis / polarity specification of anterior/posterior axis / morphogen activity / smoothened binding / cerebellar granule cell precursor proliferation / bud outgrowth involved in lung branching / striated muscle tissue development / positive regulation of immature T cell proliferation in thymus / epidermal cell fate specification / metanephric mesenchymal cell proliferation involved in metanephros development / positive regulation of hh target transcription factor activity / positive regulation of striated muscle cell differentiation / negative regulation of alpha-beta T cell differentiation / hedgehog family protein binding / determination of left/right asymmetry in lateral mesoderm / ventral midline development / lung epithelium development / artery development / smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation / formation of anatomical boundary / hindlimb morphogenesis / trachea morphogenesis / telencephalon regionalization / spinal cord motor neuron differentiation / laminin-1 binding / stem cell development / negative regulation of mesenchymal cell apoptotic process / myotube differentiation / salivary gland cavitation / intermediate filament organization / mammary gland duct morphogenesis / positive regulation of T cell differentiation in thymus / negative regulation of cholesterol efflux / neuroblast proliferation / dorsal/ventral neural tube patterning / patched binding / limb morphogenesis / somite development / cellular response to cholesterol / negative regulation of smoothened signaling pathway / negative regulation of cell division / negative regulation of transcription elongation from RNA polymerase II promoter / keratinocyte proliferation / renal system development / lymphoid progenitor cell differentiation / embryonic digestive tract morphogenesis / negative regulation of multicellular organism growth / embryonic foregut morphogenesis / limb bud formation / lung lobe morphogenesis|
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 / 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 / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy|
|Image recording||Electron dose: 50 / 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 / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 137823 / Symmetry type: POINT|
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