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- PDB-6iyc: Recognition of the Amyloid Precursor Protein by Human gamma-secretase -
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Basic information
Entry | Database: PDB / ID: 6iyc | |||||||||
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Title | Recognition of the Amyloid Precursor Protein by Human gamma-secretase | |||||||||
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![]() | MEMBRANE PROTEIN / Complex | |||||||||
Function / homology | ![]() Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / protein catabolic process at postsynapse / 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 / positive regulation of amyloid precursor protein biosynthetic process ...Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / protein catabolic process at postsynapse / 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 / 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 / dorsal/ventral neural tube patterning / regulation of synaptic vesicle cycle / neural retina development / L-glutamate import across plasma membrane / myeloid dendritic cell differentiation / Regulated proteolysis of p75NTR / regulation of phosphorylation / metanephros development / regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / brain morphogenesis / 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 / locomotion / signaling receptor activator activity / smooth endoplasmic reticulum calcium ion homeostasis / amyloid precursor protein metabolic process / axon midline choice point recognition / regulation of canonical Wnt signaling pathway / astrocyte activation involved in immune response / aggresome / regulation of long-term synaptic potentiation / regulation of spontaneous synaptic transmission / skeletal system morphogenesis / mating behavior / embryonic limb morphogenesis / NMDA selective glutamate receptor signaling pathway / cell fate specification / ciliary rootlet / myeloid cell homeostasis / regulation of postsynapse organization / azurophil granule membrane / Lysosome Vesicle Biogenesis / PTB domain binding / regulation of neuron projection development / G protein-coupled dopamine receptor signaling pathway / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / Golgi-associated vesicle / positive regulation of amyloid fibril formation / neuron remodeling / Golgi cisterna membrane / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / adult behavior / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / positive regulation of dendritic spine development / : / positive regulation of receptor recycling / mitochondrial transport / positive regulation of catalytic activity / suckling behavior / nuclear envelope lumen / blood vessel development / heart looping / protein glycosylation / dendrite development / COPII-coated ER to Golgi transport vesicle / presynaptic active zone / cerebral cortex cell migration / amyloid precursor protein catabolic process / modulation of excitatory postsynaptic potential / amyloid-beta formation / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / negative regulation of apoptotic signaling pathway / neuromuscular process controlling balance / membrane protein ectodomain proteolysis / The NLRP3 inflammasome / regulation of presynapse assembly Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / 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
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 256.3 KB | Display | ![]() |
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PDB format | ![]() | 206.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 43.7 KB | Display | |
Data in CIF | ![]() | 64.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9751MC 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.) ![]() ![]() |
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#2: Protein | Mass: 52688.551 Da / Num. of mol.: 1 / Mutation: Q112C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P49768, Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases |
#5: Protein | Mass: 11888.622 Da / Num. of mol.: 1 / Fragment: C83 / Mutation: V8C Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-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.) ![]() ![]() |
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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.) ![]() ![]() |
-Sugars , 3 types, 12 molecules ![](data/chem/img/NAG.gif)
#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, 5 molecules ![](data/chem/img/PC1.gif)
![](data/chem/img/CLR.gif)
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#9: Chemical | #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 |
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Sample preparation
Component | Name: human gamma-secretase / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
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: ![]() |
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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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 502450 / Symmetry type: POINT | ||||||||||||||||||||||||
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