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Yorodumi- PDB-6idf: Cryo-EM structure of gamma secretase in complex with a Notch fragment -
+Open data
-Basic information
Entry | Database: PDB / ID: 6idf | |||||||||
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Title | Cryo-EM structure of gamma secretase in complex with a Notch fragment | |||||||||
Components |
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Keywords | MEMBRANE PROTEIN / complex | |||||||||
Function / homology | Function and homology information 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 / retinal cone cell differentiation / venous endothelial 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 / retinal cone cell differentiation / venous endothelial cell differentiation / arterial endothelial cell differentiation / cardiac chamber formation / 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 / glomerular mesangial cell development / negative regulation of photoreceptor cell differentiation / negative regulation of cell proliferation involved in heart valve morphogenesis / regulation of somitogenesis / inhibition of neuroepithelial cell differentiation / endocardium morphogenesis / foregut morphogenesis / regulation of cell adhesion involved in heart morphogenesis / distal tubule development / MAML1-RBP-Jkappa- ICN1 complex / regulation of epithelial cell proliferation involved in prostate gland development / auditory receptor cell fate commitment / positive regulation of aorta morphogenesis / negative regulation of endothelial cell chemotaxis / atrioventricular node development / neuroendocrine cell differentiation / collecting duct development / negative regulation of extracellular matrix constituent secretion / positive regulation of transcription of Notch receptor target / cellular response to tumor cell / positive regulation of apoptotic process involved in morphogenesis / Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / compartment pattern specification / vasculogenesis involved in coronary vascular morphogenesis / amyloid precursor protein biosynthetic process / T-helper 17 type immune response / positive regulation of coagulation / negative regulation of core promoter binding / regulation of extracellular matrix assembly / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / endocardial cell differentiation / protein catabolic process at postsynapse / epithelial to mesenchymal transition involved in endocardial cushion formation / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / positive regulation of amyloid precursor protein biosynthetic process / cardiac ventricle morphogenesis / positive regulation of smooth muscle cell differentiation / positive regulation of endopeptidase activity / Noncanonical activation of NOTCH3 / mesenchymal cell development / cardiac left ventricle morphogenesis / epidermal cell fate specification / coronary vein morphogenesis / negative regulation of collagen biosynthetic process / cardiac vascular smooth muscle cell development / negative regulation of myotube differentiation / sequestering of calcium ion / Notch receptor processing / somatic stem cell division / left/right axis specification / choline transport / central nervous system myelination / synaptic vesicle targeting / negative regulation of cardiac muscle hypertrophy / membrane protein intracellular domain proteolysis / negative regulation of cell adhesion molecule production / negative regulation of axonogenesis / regulation of resting membrane potential / interleukin-17-mediated signaling pathway / positive regulation of endothelial cell differentiation / apoptotic process involved in embryonic digit morphogenesis / endocardium development / positive regulation of cardiac epithelial to mesenchymal transition / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / Pre-NOTCH Processing in Golgi / cardiac epithelial to mesenchymal transition / T cell activation involved in immune response / cellular response to follicle-stimulating hormone stimulus / pericardium morphogenesis / cardiac atrium morphogenesis / cardiac muscle cell myoblast differentiation / NOTCH4 Activation and Transmission of Signal to the Nucleus / negative regulation of catalytic activity / skin morphogenesis / negative regulation of calcium ion-dependent exocytosis / growth factor receptor binding / neuronal stem cell population maintenance / regulation of synaptic vesicle cycle / tissue regeneration / dorsal/ventral neural tube patterning 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: 2019 Title: 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. | |||||||||
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 | 6idf.cif.gz | 259.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6idf.ent.gz | 209.6 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 | 1.5 MB | Display | wwPDB validaton report |
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Full document | 6idf_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 6idf_validation.xml.gz | 45.8 KB | Display | |
Data in CIF | 6idf_validation.cif.gz | 66.3 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 (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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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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-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: 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 |
-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) |
-Processing
Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||
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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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