[English] 日本語
Yorodumi- PDB-6idf: Cryo-EM structure of gamma secretase in complex with a Notch fragment -
+Open data
-Basic information
Entry | Database: PDB / ID: 6idf | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of gamma secretase in complex with a Notch fragment | |||||||||
Components |
| |||||||||
Keywords | MEMBRANE PROTEIN / complex | |||||||||
Function / homology | Function and homology information Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / cardiac right ventricle formation / growth involved in heart morphogenesis / Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation / cell differentiation in spinal cord / retinal cone cell differentiation / venous endothelial cell differentiation / arterial endothelial cell differentiation ...Defective LFNG causes SCDO3 / coronary sinus valve morphogenesis / cardiac right atrium morphogenesis / cardiac right ventricle formation / growth involved in heart morphogenesis / Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation / cell differentiation in spinal cord / retinal cone cell differentiation / venous endothelial cell differentiation / arterial endothelial cell differentiation / cardiac chamber formation / epithelial cell fate commitment / negative regulation of pro-B cell differentiation / Pre-NOTCH Processing in the Endoplasmic Reticulum / Cajal-Retzius cell differentiation / negative regulation of inner ear auditory receptor cell differentiation / positive regulation of L-glutamate import across plasma membrane / mitral valve formation / cell migration involved in endocardial cushion formation / glomerular mesangial cell development / amyloid precursor protein biosynthetic process / negative regulation of photoreceptor cell differentiation / negative regulation of cell proliferation involved in heart valve morphogenesis / regulation of somitogenesis / inhibition of neuroepithelial cell differentiation / endocardium morphogenesis / atrioventricular node development / foregut morphogenesis / positive regulation of coagulation / regulation of cell adhesion involved in heart morphogenesis / distal tubule development / protein catabolic process at postsynapse / negative regulation of core promoter binding / MAML1-RBP-Jkappa- ICN1 complex / regulation of epithelial cell proliferation involved in prostate gland development / auditory receptor cell fate commitment / gamma-secretase complex / positive regulation of aorta morphogenesis / negative regulation of endothelial cell chemotaxis / aspartic endopeptidase activity, intramembrane cleaving / neuroendocrine cell differentiation / collecting duct development / short-term synaptic potentiation / negative regulation of extracellular matrix constituent secretion / positive regulation of transcription of Notch receptor target / positive regulation of smooth muscle cell differentiation / cellular response to tumor cell / positive regulation of amyloid precursor protein biosynthetic process / positive regulation of apoptotic process involved in morphogenesis / compartment pattern specification / vasculogenesis involved in coronary vascular morphogenesis / T-helper 17 type immune response / Noncanonical activation of NOTCH3 / positive regulation of endopeptidase activity / Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant / epithelial to mesenchymal transition involved in endocardial cushion formation / regulation of extracellular matrix assembly / endocardial cell differentiation / choline transport / cardiac ventricle morphogenesis / Notch receptor processing / central nervous system myelination / sequestering of calcium ion / cardiac left ventricle morphogenesis / mesenchymal cell development / membrane protein intracellular domain proteolysis / synaptic vesicle targeting / epidermal cell fate specification / negative regulation of collagen biosynthetic process / coronary vein morphogenesis / negative regulation of axonogenesis / cardiac vascular smooth muscle cell development / negative regulation of myotube differentiation / regulation of resting membrane potential / somatic stem cell division / left/right axis specification / negative regulation of cell adhesion molecule production / negative regulation of cardiac muscle hypertrophy / positive regulation of endothelial cell differentiation / secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development / interleukin-17-mediated signaling pathway / T cell activation involved in immune response / apoptotic process involved in embryonic digit morphogenesis / endocardium development / skin morphogenesis / positive regulation of cardiac epithelial to mesenchymal transition / NOTCH4 Activation and Transmission of Signal to the Nucleus / cardiac epithelial to mesenchymal transition / Pre-NOTCH Processing in Golgi / growth factor receptor binding / negative regulation of calcium ion-dependent exocytosis / cardiac muscle cell myoblast differentiation / cellular response to follicle-stimulating hormone stimulus / neural retina development / dorsal/ventral neural tube patterning / regulation of synaptic vesicle cycle / pericardium morphogenesis / cardiac atrium morphogenesis / negative regulation of catalytic activity / tissue regeneration Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
Authors | Yang, G. / Zhou, R. / Zhou, Q. / Guo, X. / Yan, C. / Ke, M. / Lei, J. / Shi, Y. | |||||||||
Funding support | China, 1items
| |||||||||
Citation | Journal: Nature / Year: 2019 Title: Structural basis of Notch recognition by human γ-secretase. Authors: Guanghui Yang / Rui Zhou / Qiang Zhou / Xuefei Guo / Chuangye Yan / Meng Ke / Jianlin Lei / Yigong Shi / Abstract: Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of ...Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6idf.cif.gz | 259.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb6idf.ent.gz | 209.6 KB | Display | PDB format |
PDBx/mmJSON format | 6idf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/id/6idf ftp://data.pdbj.org/pub/pdb/validation_reports/id/6idf | HTTPS FTP |
---|
-Related structure data
Related structure data | 9648MC M: map data used to model this data C: citing same article (ref.) |
---|---|
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 / Production host: Homo sapiens (human) / References: UniProt: Q92542 |
---|---|
#2: Protein | Mass: 52644.543 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PS1 / Production host: Homo sapiens (human) References: UniProt: P49768, Hydrolases; Acting on peptide bonds (peptidases); Aspartic endopeptidases |
#5: Protein | Mass: 14758.500 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Homo sapiens (human) / References: UniProt: P46531*PLUS |
-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 / 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: PEN2 / 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, 7 molecules
#9: Chemical | ChemComp-PC1 / #10: Chemical | |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: gamma-secretaseGamma 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 FIELDBright-field microscopy |
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 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 476853 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|