|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) / Sterol-sensing domain (SSD) profile. / Patched family / Transmembrane receptor, patched / Protein patched/dispatched / Activation of SMO / Hedgehog 'on' state / Sterol-sensing domain / Hedgehog 'off' state / Ligand-receptor interactions ...Class B/2 (Secretin family receptors) / Sterol-sensing domain (SSD) profile. / Patched family / Transmembrane receptor, patched / Protein patched/dispatched / Activation of SMO / Hedgehog 'on' state / Sterol-sensing domain / Hedgehog 'off' state / Ligand-receptor interactions / hedgehog receptor activity / neural plate axis specification / response to chlorate / 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 / somite development / limb morphogenesis / negative regulation of multicellular organism growth / cellular response to cholesterol / negative regulation of smoothened signaling pathway / negative regulation of cell division / positive regulation of cholesterol efflux / renal system development / keratinocyte proliferation / dorsal/ventral pattern formation / pharyngeal system development / positive regulation of epidermal cell differentiation / mammary gland epithelial cell differentiation / cell fate determination / commissural neuron axon guidance / 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 / negative regulation of epithelial cell proliferation / heart morphogenesis / dendritic growth cone / axonal growth cone / protein localization to plasma membrane / regulation of mitotic cell cycle / protein processing / cyclin binding / response to retinoic acid / animal organ morphogenesis / regulation of protein localization / neural tube closure / liver regeneration / response to mechanical stimulus / 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 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
|#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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