+Open data
-Basic information
Entry | Database: PDB / ID: 6dmb | |||||||||
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Title | Cryo-EM structure of human Ptch1 | |||||||||
Components | Protein patched homolog 1 | |||||||||
Keywords | PROTEIN BINDING / Receptor / RND family | |||||||||
Function / homology | Function and homology information neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / smoothened binding / neural tube patterning / hedgehog family protein binding / Ligand-receptor interactions / hindlimb morphogenesis ...neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / smoothened binding / neural tube patterning / hedgehog family protein binding / Ligand-receptor interactions / hindlimb morphogenesis / epidermal cell fate specification / spinal cord motor neuron differentiation / prostate gland development / Activation of SMO / negative regulation of cell division / patched binding / limb morphogenesis / somite development / dorsal/ventral neural tube patterning / cellular response to cholesterol / smooth muscle tissue development / pharyngeal system development / mammary gland duct morphogenesis / mammary gland epithelial cell differentiation / cell fate determination / commissural neuron axon guidance / metanephric collecting duct development / regulation of smoothened signaling pathway / dorsal/ventral pattern formation / Class B/2 (Secretin family receptors) / embryonic limb morphogenesis / cholesterol binding / ciliary membrane / smoothened signaling pathway / negative regulation of multicellular organism growth / branching involved in ureteric bud morphogenesis / positive regulation of epidermal cell differentiation / spermatid development / regulation of mitotic cell cycle / dendritic growth cone / positive regulation of cholesterol efflux / keratinocyte proliferation / negative regulation of keratinocyte proliferation / negative regulation of osteoblast differentiation / embryonic organ development / Hedgehog 'off' state / negative regulation of smoothened signaling pathway / axonal growth cone / response to mechanical stimulus / heart morphogenesis / response to retinoic acid / negative regulation of stem cell proliferation / cyclin binding / stem cell proliferation / neural tube closure / liver regeneration / caveola / protein localization to plasma membrane / animal organ morphogenesis / Hedgehog 'on' state / brain development / negative regulation of DNA-binding transcription factor activity / protein processing / endocytic vesicle membrane / regulation of protein localization / glucose homeostasis / response to estradiol / apical part of cell / heparin binding / midbody / in utero embryonic development / response to xenobiotic stimulus / intracellular membrane-bounded organelle / protein-containing complex binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||
Authors | Yan, N. / Gong, X. / Qian, H.W. | |||||||||
Funding support | China, 2items
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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. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6dmb.cif.gz | 200.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6dmb.ent.gz | 155.3 KB | Display | PDB format |
PDBx/mmJSON format | 6dmb.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/dm/6dmb ftp://data.pdbj.org/pub/pdb/validation_reports/dm/6dmb | HTTPS FTP |
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-Related structure data
Related structure data | 7963MC 7964C 7968C 6dmoC 6dmyC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 150189.578 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTCH1, PTCH / Production host: Homo sapiens (human) / References: UniProt: Q13635 | ||
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#2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source | ||
#3: Sugar | ChemComp-NAG / #4: Chemical | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Patch1 / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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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
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | 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) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 94445 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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