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Yorodumi- EMDB-9648: Cryo-EM structure of gamma secretase in complex with a Notch fragment -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9648 | |||||||||
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Title | Cryo-EM structure of gamma secretase in complex with a Notch fragment | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information Defective LFNG causes SCDO3 / positive regulation of L-glutamate import across plasma membrane / Cajal-Retzius cell differentiation / 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 ...Defective LFNG causes SCDO3 / positive regulation of L-glutamate import across plasma membrane / Cajal-Retzius cell differentiation / 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 / amyloid precursor protein biosynthetic process / 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 / positive regulation of coagulation / protein catabolic process at postsynapse / negative regulation of core promoter binding / 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 / gamma-secretase complex / inhibition of neuroepithelial cell differentiation / endocardium morphogenesis / atrioventricular node development / foregut morphogenesis / regulation of cell adhesion involved in heart morphogenesis / distal tubule development / MAML1-RBP-Jkappa- ICN1 complex / aspartic endopeptidase activity, intramembrane cleaving / regulation of epithelial cell proliferation involved in prostate gland development / short-term synaptic potentiation / auditory receptor cell fate commitment / positive regulation of aorta morphogenesis / negative regulation of endothelial cell chemotaxis / neuroendocrine cell differentiation / collecting duct development / negative regulation of extracellular matrix constituent secretion / positive regulation of transcription of Notch receptor target / positive regulation of amyloid precursor protein biosynthetic process / positive regulation of smooth muscle cell differentiation / cellular response to tumor cell / positive regulation of apoptotic process involved in morphogenesis / choline transport / compartment pattern specification / Noncanonical activation of NOTCH3 / positive regulation of endopeptidase activity / vasculogenesis involved in coronary vascular morphogenesis / T-helper 17 type immune response / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / epithelial to mesenchymal transition involved in endocardial cushion formation / Notch receptor processing / regulation of extracellular matrix assembly / endocardial cell differentiation / cardiac ventricle morphogenesis / central nervous system myelination / sequestering of calcium ion / membrane protein intracellular domain proteolysis / mesenchymal cell development / synaptic vesicle targeting / cardiac left ventricle morphogenesis / epidermal cell fate specification / negative regulation of axonogenesis / negative regulation of collagen biosynthetic process / coronary vein morphogenesis / regulation of resting membrane potential / cardiac vascular smooth muscle cell development / negative regulation of myotube differentiation / somatic stem cell division / left/right axis specification / negative regulation of cell adhesion molecule production / negative regulation of cardiac muscle hypertrophy / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / T cell activation involved in immune response / positive regulation of endothelial cell differentiation / interleukin-17-mediated signaling pathway / apoptotic process involved in embryonic digit morphogenesis / endocardium development / skin morphogenesis / NOTCH4 Activation and Transmission of Signal to the Nucleus / positive regulation of cardiac epithelial to mesenchymal transition / cardiac epithelial to mesenchymal transition / Pre-NOTCH Processing in Golgi / growth factor receptor binding / neural retina development / regulation of synaptic vesicle cycle / dorsal/ventral neural tube patterning / cellular response to follicle-stimulating hormone stimulus / negative regulation of calcium ion-dependent exocytosis / cardiac muscle cell myoblast differentiation / pericardium morphogenesis / cardiac atrium morphogenesis / negative regulation of catalytic activity / L-glutamate import across plasma membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | 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 | |||||||||
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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9648.map.gz | 117.1 MB | EMDB map data format | |
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Header (meta data) | emd-9648-v30.xml emd-9648.xml | 18.8 KB 18.8 KB | Display Display | EMDB header |
Images | emd_9648.png | 69.8 KB | ||
Others | emd_9648_additional.map.gz | 111.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9648 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9648 | HTTPS FTP |
-Related structure data
Related structure data | 6idfMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9648.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.091 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: #1
File | emd_9648_additional.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : gamma-secretase
+Supramolecule #1: gamma-secretase
+Macromolecule #1: Nicastrin
+Macromolecule #2: Presenilin-1
+Macromolecule #3: Gamma-secretase subunit APH-1A
+Macromolecule #4: Gamma-secretase subunit PEN-2
+Macromolecule #5: Notch1
+Macromolecule #6: N-ACETYL-D-GLUCOSAMINE
+Macromolecule #7: BETA-D-MANNOSE
+Macromolecule #8: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+Macromolecule #9: CHOLESTEROL
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.5625 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: PROJECTION MATCHING |
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Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 476853 |