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Yorodumi- PDB-8kco: Cryo-EM structure of human gamma-secretase in complex with RO4929097 -
+Open data
-Basic information
Entry | Database: PDB / ID: 8kco | ||||||
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Title | Cryo-EM structure of human gamma-secretase in complex with RO4929097 | ||||||
Components |
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Keywords | MEMBRANE PROTEIN / Intramembrane protease / gamma-secretase / gamma-secretase inhibitor / MEMBRANE PROTEIN-HYDROLASE complex | ||||||
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 / brain morphogenesis / endoplasmic reticulum calcium ion homeostasis / nuclear outer membrane / glutamate receptor signaling pathway / locomotion / 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 / embryonic limb morphogenesis / skeletal system morphogenesis / cell fate specification / ciliary rootlet / myeloid cell homeostasis / regulation of postsynapse organization / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / positive regulation of amyloid fibril formation / Golgi cisterna membrane / adult behavior / mitochondrial transport / positive regulation of dendritic spine development / positive regulation of receptor recycling / blood vessel development / regulation of neuron projection development / heart looping / protein glycosylation / amyloid precursor protein catabolic process / amyloid-beta formation / negative regulation of apoptotic signaling pathway / membrane protein ectodomain proteolysis / endopeptidase activator activity / autophagosome assembly / EPH-ephrin mediated repulsion of cells / smooth endoplasmic reticulum / neuron development / hematopoietic progenitor cell differentiation / negative regulation of ubiquitin-dependent protein catabolic process / somitogenesis / calcium ion homeostasis / T cell proliferation / Nuclear signaling by ERBB4 / rough endoplasmic reticulum / epithelial cell proliferation / Notch signaling pathway / regulation of synaptic transmission, glutamatergic / neuron projection maintenance / NOTCH2 Activation and Transmission of Signal to the Nucleus / cellular response to calcium ion / astrocyte activation / NOTCH3 Activation and Transmission of Signal to the Nucleus / Degradation of the extracellular matrix / positive regulation of glycolytic process / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / cerebellum development / post-embryonic development / thymus development / negative regulation of protein phosphorylation / dendritic shaft / PDZ domain binding / apoptotic signaling pathway / cell-cell adhesion / synapse organization Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Guo, X. / Li, H. / Kai, U. / Yan, C. / Lei, J. / Zhou, R. / Shi, Y. | ||||||
Funding support | China, 1items
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Citation | Journal: To Be Published Title: CryoEM structure of PS1-containing gamma-secretase in complex with MRK-560 Authors: Guo, X. / Wang, Y. / Zhou, J. / Jin, C. / Wang, J. / Jia, B. / Jing, D. / Yan, C. / Lei, J. / Zhou, R. / Shi, Y. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8kco.cif.gz | 257.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8kco.ent.gz | 202 KB | Display | PDB format |
PDBx/mmJSON format | 8kco.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8kco_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 8kco_full_validation.pdf.gz | 1.8 MB | Display | |
Data in XML | 8kco_validation.xml.gz | 51.6 KB | Display | |
Data in CIF | 8kco_validation.cif.gz | 73.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/kc/8kco ftp://data.pdbj.org/pub/pdb/validation_reports/kc/8kco | HTTPS FTP |
-Related structure data
Related structure data | 37106MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 77622.617 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NCSTN, KIAA0253, UNQ1874/PRO4317 / Production host: Homo sapiens (human) / References: UniProt: Q92542 |
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#2: Protein | Mass: 52713.535 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PSEN1, AD3, PS1, PSNL1 / Production host: Homo sapiens (human) References: UniProt: P49768, Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases |
-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, PSF, CGI-78, UNQ579/PRO1141 / 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: PSENEN, PEN2, MDS033 / Production host: Homo sapiens (human) / References: UniProt: Q9NZ42 |
-Sugars , 3 types, 12 molecules
#5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: 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 #7: Sugar | ChemComp-NAG / |
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-Non-polymers , 3 types, 6 molecules
#8: Chemical | ChemComp-N60 / Mass: 469.405 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H20F5N3O3 / Feature type: SUBJECT OF INVESTIGATION | ||
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#9: Chemical | #10: Chemical | |
-Details
Has ligand of interest | Y |
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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: Cryo-EM structure of human gamma-secretase in complex with RO4929097 Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
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 / Nominal defocus max: 1800 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 5551418 / Symmetry type: POINT | ||||||||||||||||||||||||
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