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Yorodumi- PDB-6idf: Cryo-EM structure of gamma secretase in complex with a Notch fragment -
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Open data
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Basic information
| Entry | Database: PDB / ID: 6idf | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | Cryo-EM structure of gamma secretase in complex with a Notch fragment | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Keywords | MEMBRANE PROTEIN / complex | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationDefective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / cardiac right ventricle formation / growth involved in heart morphogenesis / Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation / cell differentiation in spinal cord / venous endothelial cell differentiation / retinal cone cell differentiation / arterial endothelial cell differentiation ...Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / cardiac right ventricle formation / growth involved in heart morphogenesis / Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation / cell differentiation in spinal cord / venous endothelial cell differentiation / retinal cone cell differentiation / arterial endothelial cell differentiation / epithelial cell fate commitment / negative regulation of pro-B cell differentiation / Pre-NOTCH Processing in the Endoplasmic Reticulum / negative regulation of inner ear auditory receptor cell differentiation / mitral valve formation / cell migration involved in endocardial cushion formation / negative regulation of photoreceptor cell differentiation / negative regulation of cell proliferation involved in heart valve morphogenesis / regulation of somitogenesis / endocardium morphogenesis / foregut morphogenesis / distal tubule development / inhibition of neuroepithelial cell differentiation / MAML1-RBP-Jkappa- ICN1 complex / regulation of epithelial cell proliferation involved in prostate gland development / cardiac chamber formation / auditory receptor cell fate commitment / negative regulation of endothelial cell chemotaxis / atrioventricular node development / positive regulation of transcription of Notch receptor target / neuroendocrine cell differentiation / positive regulation of aorta morphogenesis / Cajal-Retzius cell differentiation / cellular response to tumor cell / positive regulation of L-glutamate import across plasma membrane / negative regulation of extracellular matrix constituent secretion / collecting duct development / compartment pattern specification / amyloid precursor protein biosynthetic process / negative regulation of core promoter binding / positive regulation of apoptotic process involved in morphogenesis / positive regulation of endopeptidase activity / vasculogenesis involved in coronary vascular morphogenesis / gamma-secretase complex / regulation of extracellular matrix assembly / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / endocardial cell differentiation / chemical synaptic transmission, postsynaptic / positive regulation of amyloid precursor protein biosynthetic process / epithelial to mesenchymal transition involved in endocardial cushion formation / T-helper 17 type immune response / smooth endoplasmic reticulum calcium ion homeostasis / cardiac ventricle morphogenesis / Noncanonical activation of NOTCH3 / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / protein catabolic process at postsynapse / positive regulation of smooth muscle cell differentiation / epidermal cell fate specification / mesenchymal cell development / TGFBR3 PTM regulation / coronary vein morphogenesis / cardiac left ventricle morphogenesis / sequestering of calcium ion / cardiac vascular smooth muscle cell development / negative regulation of myotube differentiation / left/right axis specification / Notch receptor processing / synaptic vesicle targeting / positive regulation of coagulation / central nervous system myelination / negative regulation of axonogenesis / negative regulation of catalytic activity / glomerular mesangial cell development / somatic stem cell division / negative regulation of cell adhesion molecule production / membrane protein intracellular domain proteolysis / endocardium development / apoptotic process involved in embryonic digit morphogenesis / regulation of cell adhesion involved in heart morphogenesis / negative regulation of cardiac muscle hypertrophy / interleukin-17-mediated signaling pathway / positive regulation of endothelial cell differentiation / positive regulation of cardiac epithelial to mesenchymal transition / cardiac epithelial to mesenchymal transition / Pre-NOTCH Processing in Golgi / pericardium morphogenesis / skin morphogenesis / cardiac atrium morphogenesis / choline transport / T cell activation involved in immune response / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / negative regulation of collagen biosynthetic process / neuronal stem cell population maintenance / cardiac muscle cell myoblast differentiation / cellular response to follicle-stimulating hormone stimulus / NOTCH4 Activation and Transmission of Signal to the Nucleus / dorsal/ventral neural tube patterning / ciliary rootlet / negative regulation of calcium ion-dependent exocytosis Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Yang, G. / Zhou, R. / Zhou, Q. / Guo, X. / Yan, C. / Ke, M. / Lei, J. / Shi, Y. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Funding support | China, 1items
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Citation | Journal: Nature / Year: 2019Title: Structural basis of Notch recognition by human γ-secretase. Authors: Guanghui Yang / Rui Zhou / Qiang Zhou / Xuefei Guo / Chuangye Yan / Meng Ke / Jianlin Lei / Yigong Shi / ![]() Abstract: Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of ...Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 6idf.cif.gz | 268.3 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb6idf.ent.gz | 209.8 KB | Display | PDB format |
| PDBx/mmJSON format | 6idf.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 6idf_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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| Full document | 6idf_full_validation.pdf.gz | 1.6 MB | Display | |
| Data in XML | 6idf_validation.xml.gz | 45.8 KB | Display | |
| Data in CIF | 6idf_validation.cif.gz | 67.2 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/id/6idf ftp://data.pdbj.org/pub/pdb/validation_reports/id/6idf | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9648MC M: map data used to model this data C: citing same article ( |
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| Similar structure data |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Protein , 3 types, 3 molecules ABE
| #1: Protein | Mass: 78483.570 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NCSTN / Production host: Homo sapiens (human) / References: UniProt: Q92542 |
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| #2: Protein | Mass: 52644.543 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PS1 / Production host: Homo sapiens (human)References: UniProt: P49768, Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases |
| #5: Protein | Mass: 14758.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: UniProt: P46531*PLUS |
-Gamma-secretase subunit ... , 2 types, 2 molecules CD
| #3: Protein | Mass: 29017.943 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: APH1A / Production host: Homo sapiens (human) / References: UniProt: Q96BI3 |
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| #4: Protein | Mass: 12038.029 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PEN2 / Production host: Homo sapiens (human) / References: UniProt: Q9NZ42 |
-Sugars , 3 types, 12 molecules 
| #6: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #7: Polysaccharide | beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #8: Sugar | ChemComp-NAG / |
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-Non-polymers , 2 types, 7 molecules 


| #9: Chemical | ChemComp-PC1 / #10: Chemical | |
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-Details
| Has protein modification | Y |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: gamma-secretase / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 7.4 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Cryogen name: ETHANE |
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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 FIELD |
| Image recording | Electron dose: 1.5625 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
| Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||
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| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 476853 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi



Homo sapiens (human)
China, 1items
Citation
UCSF Chimera














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