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- EMDB-9751: Recognition of the Amyloid Precursor Protein by Human gamma-secretase -
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Open data
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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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Function / homology | ![]() 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 / endoplasmic reticulum calcium ion homeostasis / microglia development / 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 / nuclear outer membrane / glutamate receptor signaling pathway / signaling receptor activator activity / locomotion / amyloid precursor protein metabolic process / regulation of canonical Wnt signaling pathway / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / aggresome / astrocyte activation involved in immune response / regulation of long-term synaptic potentiation / regulation of spontaneous synaptic transmission / embryonic limb morphogenesis / mating behavior / skeletal system morphogenesis / cell fate specification / NMDA selective glutamate receptor signaling pathway / myeloid cell homeostasis / ciliary rootlet / regulation of postsynapse organization / azurophil granule membrane / Lysosome Vesicle Biogenesis / 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 / Golgi cisterna membrane / positive regulation of amyloid fibril formation / adult behavior / mitochondrial transport / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of dendritic spine development / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / positive regulation of receptor recycling / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / blood vessel development / regulation of neuron projection development / suckling behavior / 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 / negative regulation of apoptotic signaling pathway / The NLRP3 inflammasome / membrane protein ectodomain proteolysis / regulation of presynapse assembly Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
![]() | Zhou R / Yang G / Guo X / Zhou Q / Lei J / Shi Y | |||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 111.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.7 KB 15.7 KB | Display Display | ![]() |
Images | ![]() | 175.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6iycMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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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
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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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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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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: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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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 |