|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. / Sterol-sensing domain / Hedgehog ligand biogenesis / Hedgehog 'off' state / Ligand-receptor interactions / Class B/2 (Secretin family receptors) / Hedgehog 'on' state / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Release of Hh-Np from the secreting cell ...Intein N-terminal splicing motif profile. / Sterol-sensing domain / Hedgehog ligand biogenesis / Hedgehog 'off' state / Ligand-receptor interactions / Class B/2 (Secretin family receptors) / Hedgehog 'on' state / Activation of SMO / HHAT G278V abrogates palmitoylation of Hh-Np / Release of Hh-Np from the secreting cell / Hh mutants that don't undergo autocatalytic processing are degraded by ERAD / Hedgehog, N-terminal signalling 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 / neural plate axis specification / hedgehog receptor activity / cell proliferation involved in metanephros development / response to chlorate / cell differentiation involved in kidney development / smoothened signaling pathway involved in dorsal/ventral neural tube patterning / neural tube patterning / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of skeletal muscle cell proliferation / positive regulation of kidney smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / positive regulation of sclerotome development / right lung development / left lung development / primary prostatic bud elongation / epithelial-mesenchymal signaling involved in prostate gland development / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / smoothened binding / regulation of prostatic bud formation / regulation of odontogenesis / 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 / morphogen activity / cerebellar granule cell precursor proliferation / bud outgrowth involved in lung branching / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / epidermal cell fate specification / positive regulation of immature T cell proliferation in thymus / hedgehog family protein binding / metanephric mesenchymal cell proliferation involved in metanephros development / determination of left/right asymmetry in lateral mesoderm / positive regulation of striated muscle cell differentiation / negative regulation of alpha-beta T cell differentiation / lung epithelium development / ventral midline development / positive regulation of hh target transcription factor activity / 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 / negative regulation of mesenchymal cell apoptotic process / myotube differentiation / salivary gland cavitation / intermediate filament organization / mammary gland duct morphogenesis / stem cell development / negative regulation of cholesterol efflux / pattern specification process / positive regulation of T cell differentiation in thymus / lymphoid progenitor cell differentiation / dorsal/ventral neural tube patterning / patched binding / neuroblast proliferation / negative regulation of multicellular organism growth / limb morphogenesis / somite development / 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 cryo-EM structures of human ...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 cryo-EM structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 Å and 3.6 Å, respectively. Ptch1 comprises two interacting extracellular domains ECD1 and ECD2 and twelve transmembrane segments (TMs), with TMs 2-6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2, and the other on the membrane-facing cavity of 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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