[English] 日本語
Yorodumi- PDB-6iyc: Recognition of the Amyloid Precursor Protein by Human gamma-secretase -
+
Open data
-
Basic information
| Entry | Database: PDB / ID: 6iyc | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | Recognition of the Amyloid Precursor Protein by Human gamma-secretase | |||||||||||||||||||||||||||||||||||||||
Components |
| |||||||||||||||||||||||||||||||||||||||
Keywords | MEMBRANE PROTEIN / Complex | |||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationCajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / negative regulation of core promoter binding / positive regulation of endopeptidase activity / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / positive regulation of amyloid precursor protein biosynthetic process / smooth endoplasmic reticulum calcium ion homeostasis ...Cajal-Retzius cell differentiation / positive regulation of L-glutamate import across plasma membrane / amyloid precursor protein biosynthetic process / negative regulation of core promoter binding / positive regulation of endopeptidase activity / gamma-secretase complex / aspartic endopeptidase activity, intramembrane cleaving / short-term synaptic potentiation / positive regulation of amyloid precursor protein biosynthetic process / smooth endoplasmic reticulum calcium ion homeostasis / Noncanonical activation of NOTCH3 / protein catabolic process at postsynapse / TGFBR3 PTM regulation / sequestering of calcium ion / Notch receptor processing / synaptic vesicle targeting / positive regulation of coagulation / central nervous system myelination / negative regulation of axonogenesis / membrane protein intracellular domain proteolysis / skin morphogenesis / choline transport / T cell activation involved in immune response / NOTCH4 Activation and Transmission of Signal to the Nucleus / dorsal/ventral neural tube patterning / ciliary rootlet / neural retina development / regulation of resting membrane potential / L-glutamate import across plasma membrane / Regulated proteolysis of p75NTR / regulation of phosphorylation / myeloid dendritic cell differentiation / metanephros development / amyloid-beta complex / growth cone lamellipodium / endoplasmic reticulum calcium ion homeostasis / brain morphogenesis / cellular response to norepinephrine stimulus / growth cone filopodium / locomotion / microglia development / amyloid precursor protein metabolic process / collateral sprouting in absence of injury / regulation of synaptic vesicle cycle / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of long-term synaptic potentiation / axo-dendritic transport / regulation of Wnt signaling pathway / regulation of synapse structure or activity / regulation of postsynapse organization / axon midline choice point recognition / astrocyte activation involved in immune response / embryonic limb morphogenesis / cell fate specification / regulation of canonical Wnt signaling pathway / NMDA selective glutamate receptor signaling pathway / regulation of spontaneous synaptic transmission / mating behavior / myeloid cell homeostasis / aggresome / growth factor receptor binding / skeletal system morphogenesis / Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases / peptidase activator activity / azurophil granule membrane / G protein-coupled dopamine receptor signaling pathway / Golgi cisterna membrane / glutamate receptor signaling pathway / Golgi-associated vesicle / PTB domain binding / positive regulation of amyloid fibril formation / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / Lysosome Vesicle Biogenesis / astrocyte projection / neuron remodeling / : / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / blood vessel development / amyloid-beta formation / mitochondrial transport / amyloid precursor protein catabolic process / heart looping / nuclear envelope lumen / regulation of neuron projection development / positive regulation of dendritic spine development / adult behavior / positive regulation of receptor recycling / dendrite development / cerebral cortex cell migration / positive regulation of protein metabolic process / smooth endoplasmic reticulum / nuclear outer membrane / TRAF6 mediated NF-kB activation / membrane protein ectodomain proteolysis / Advanced glycosylation endproduct receptor signaling / signaling receptor activator activity / negative regulation of long-term synaptic potentiation / modulation of excitatory postsynaptic potential / negative regulation of apoptotic signaling pathway / The NLRP3 inflammasome Similarity search - Function | |||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / 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, 1items
| |||||||||||||||||||||||||||||||||||||||
Citation | Journal: Science / Year: 2019Title: 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 |
|
-
Structure visualization
| Movie |
Movie viewer |
|---|---|
| Structure viewer | Molecule: Molmil Jmol/JSmol |
-
Downloads & links
-
Download
| PDBx/mmCIF format | 6iyc.cif.gz | 265.3 KB | Display | PDBx/mmCIF format |
|---|---|---|---|---|
| PDB format | pdb6iyc.ent.gz | 206.8 KB | Display | PDB format |
| PDBx/mmJSON format | 6iyc.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 6iyc_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
|---|---|---|---|---|
| Full document | 6iyc_full_validation.pdf.gz | 1.5 MB | Display | |
| Data in XML | 6iyc_validation.xml.gz | 43 KB | Display | |
| Data in CIF | 6iyc_validation.cif.gz | 65.4 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/iy/6iyc ftp://data.pdbj.org/pub/pdb/validation_reports/iy/6iyc | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9751MC M: map data used to model this data C: citing same article ( |
|---|---|
| Similar structure data |
-
Links
-
Assembly
| Deposited unit | ![]()
|
|---|---|
| 1 |
|
-
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.) Homo sapiens (human) / Gene: NCSTN, KIAA0253, UNQ1874/PRO4317 / Production host: Homo sapiens (human) / References: UniProt: Q92542 |
|---|---|
| #2: Protein | Mass: 52688.551 Da / Num. of mol.: 1 / Mutation: Q112C 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 |
| #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.) Homo sapiens (human) / Gene: APP, A4, AD1 / Production host: Homo sapiens (human) / References: UniProt: P05067 |
-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 |
|---|---|
| #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 
| #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 / |
|---|
-Non-polymers , 2 types, 5 molecules 


| #9: Chemical | | #10: Chemical | |
|---|
-Details
| Has protein modification | Y |
|---|
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
|---|---|
| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
| Component | Name: human gamma-secretase / Type: COMPLEX / Entity ID: #1-#5 / Source: RECOMBINANT |
|---|---|
| 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 |
|---|---|
| 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 |
| Image recording | Electron dose: 1.5625 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
| Software | Name: PHENIX / Version: 1.13_2998: / Classification: refinement | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 502450 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
|
Movie
Controller
About Yorodumi



Homo sapiens (human)
China, 1items
Citation
UCSF Chimera










PDBj
































