|Entry||Database: PDB / ID: 6dmo|
|Title||Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L|
|Components||Protein patched homolog 1|
|Keywords||PROTEIN BINDING / Receptor / RND family|
|Function / homology||Class B/2 (Secretin family receptors) / Activation of SMO / Hedgehog 'off' state / Sterol-sensing domain / Hedgehog 'on' state / Ligand-receptor interactions / Sterol-sensing domain (SSD) profile. / Protein patched/dispatched / Transmembrane receptor, patched / Patched family ...Class B/2 (Secretin family receptors) / Activation of SMO / Hedgehog 'off' state / Sterol-sensing domain / Hedgehog 'on' state / Ligand-receptor interactions / Sterol-sensing domain (SSD) profile. / Protein patched/dispatched / Transmembrane receptor, patched / Patched family / neural plate axis specification / response to chlorate / 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 / smoothened binding / epidermal cell fate specification / hedgehog family protein binding / hindlimb morphogenesis / spinal cord motor neuron differentiation / mammary gland duct morphogenesis / patched binding / negative regulation of multicellular organism growth / somite development / limb morphogenesis / negative regulation of cell division / cellular response to cholesterol / negative regulation of smoothened signaling pathway / renal system development / positive regulation of cholesterol efflux / keratinocyte proliferation / pharyngeal system development / dorsal/ventral pattern formation / commissural neuron axon guidance / positive regulation of epidermal cell differentiation / mammary gland epithelial cell differentiation / cell fate determination / ciliary membrane / smoothened signaling pathway / prostate gland development / regulation of smoothened signaling pathway / embryonic limb morphogenesis / cholesterol binding / embryonic organ development / branching involved in ureteric bud morphogenesis / negative regulation of osteoblast differentiation / heart morphogenesis / dendritic growth cone / negative regulation of epithelial cell proliferation / axonal growth cone / protein localization to plasma membrane / cyclin binding / protein processing / response to retinoic acid / animal organ morphogenesis / regulation of protein localization / neural tube closure / response to mechanical stimulus / liver regeneration / regulation of mitotic cell cycle / endocytic vesicle membrane / caveola / brain development / midbody / negative regulation of DNA-binding transcription factor activity / in utero embryonic development / glucose homeostasis / response to estradiol / heparin binding / postsynaptic density / protein-containing complex binding / response to drug / intracellular membrane-bounded organelle / positive regulation of transcription, DNA-templated / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / integral component of membrane / plasma membrane / nucleus / Protein patched homolog 1|
Function and homology information
|Specimen source||Homo sapiens (human)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / 4.1 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
|#1: Protein/peptide|| |
Mass: 150266.656 Da / Num. of mol.: 1 / Mutation: L282Q, T500F, P504L / Source: (gene. exp.) Homo sapiens (human) / Gene: PTCH1, PTCH / Production host: Homo sapiens (human) / References: UniProt: Q13635
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / Reconstruction method: single particle reconstruction|
|Component||Name: Patch1 with L282Q/T500F/P504L mutations / 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: 1.13_2998: / Classification: refinement|
|CTF correction||Type: PHASE FLIPPING AND AMPLITUDE CORRECTION|
|3D reconstruction||Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Number of particles: 154721 / Symmetry type: POINT|
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