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Yorodumi- EMDB-9751: Recognition of the Amyloid Precursor Protein by Human gamma-secretase -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9751 | |||||||||
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Title | Recognition of the Amyloid Precursor Protein by Human gamma-secretase | |||||||||
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Sample |
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Function / homology | Function and homology information Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / positive regulation of coagulation / negative regulation of core promoter binding / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / protein catabolic process at postsynapse / positive regulation of amyloid precursor protein biosynthetic process ...Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / positive regulation of coagulation / negative regulation of core promoter binding / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / protein catabolic process at postsynapse / positive regulation of amyloid precursor protein biosynthetic process / positive regulation of endopeptidase activity / Noncanonical activation of NOTCH3 / sequestering of calcium ion / Notch receptor processing / choline transport / central nervous system myelination / synaptic vesicle targeting / membrane protein intracellular domain proteolysis / negative regulation of axonogenesis / regulation of resting membrane potential / T cell activation involved in immune response / NOTCH4 Activation and Transmission of Signal to the Nucleus / skin morphogenesis / growth factor receptor binding / regulation of synaptic vesicle cycle / dorsal/ventral neural tube patterning / neural retina development / L-glutamate import across plasma membrane / myeloid dendritic cell differentiation / Regulated proteolysis of p75NTR / cerebral cortex cell migration / regulation of phosphorylation / metanephros development / regulation of epidermal growth factor-activated receptor activity / brain morphogenesis / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / endoplasmic reticulum calcium ion homeostasis / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / nuclear outer membrane / glutamate receptor signaling pathway / locomotion / axon midline choice point recognition / amyloid precursor protein metabolic process / smooth endoplasmic reticulum calcium ion homeostasis / regulation of canonical Wnt signaling pathway / astrocyte activation involved in immune response / aggresome / regulation of long-term synaptic potentiation / regulation of spontaneous synaptic transmission / mating behavior / embryonic limb morphogenesis / skeletal system morphogenesis / cell fate specification / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / myeloid cell homeostasis / regulation of postsynapse organization / Lysosome Vesicle Biogenesis / azurophil granule membrane / PTB domain binding / G protein-coupled dopamine receptor signaling pathway / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / Golgi cisterna membrane / adult behavior / positive regulation of G2/M transition of mitotic cell cycle / mitochondrial transport / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / positive regulation of dendritic spine development / positive regulation of receptor recycling / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / blood vessel development / regulation of neuron projection development / heart looping / protein glycosylation / dendrite development / amyloid precursor protein catabolic process / presynaptic active zone / modulation of excitatory postsynaptic potential / regulation of peptidyl-tyrosine phosphorylation / amyloid-beta formation / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / negative regulation of apoptotic signaling pathway / membrane protein ectodomain proteolysis / regulation of presynapse assembly Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
Authors | Zhou R / Yang G / Guo X / Zhou Q / Lei J / Shi Y | |||||||||
Funding support | China, 1 items
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Citation | Journal: Science / Year: 2019 Title: Recognition of the amyloid precursor protein by human γ-secretase. Authors: Rui Zhou / Guanghui Yang / Xuefei Guo / Qiang Zhou / Jianlin Lei / Yigong Shi / Abstract: Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a ...Cleavage of amyloid precursor protein (APP) by the intramembrane protease γ-secretase is linked to Alzheimer's disease (AD). We report an atomic structure of human γ-secretase in complex with a transmembrane (TM) APP fragment at 2.6-angstrom resolution. The TM helix of APP closely interacts with five surrounding TMs of PS1 (the catalytic subunit of γ-secretase). A hybrid β sheet, which is formed by a β strand from APP and two β strands from PS1, guides γ-secretase to the scissile peptide bond of APP between its TM and β strand. Residues at the interface between PS1 and APP are heavily targeted by recurring mutations from AD patients. This structure, together with that of γ-secretase bound to Notch, reveal contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors. | |||||||||
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_9751.map.gz | 111.6 MB | EMDB map data format | |
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Header (meta data) | emd-9751-v30.xml emd-9751.xml | 15.7 KB 15.7 KB | Display Display | EMDB header |
Images | emd_9751.png | 175.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9751 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9751 | HTTPS FTP |
-Validation report
Summary document | emd_9751_validation.pdf.gz | 460.7 KB | Display | EMDB validaton report |
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Full document | emd_9751_full_validation.pdf.gz | 460.3 KB | Display | |
Data in XML | emd_9751_validation.xml.gz | 6.4 KB | Display | |
Data in CIF | emd_9751_validation.cif.gz | 7.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9751 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9751 | HTTPS FTP |
-Related structure data
Related structure data | 6iycMC 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_9751.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
-Sample components
+Entire : human gamma-secretase
+Supramolecule #1: human 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: Amyloid-beta A4 protein
+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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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 1.5625 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 502450 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |