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- PDB-6q2j: Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15 -
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Open data
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Basic information
Entry | Database: PDB / ID: 6q2j | ||||||
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Title | Cryo-EM structure of extracellular dimeric complex of RET/GFRAL/GDF15 | ||||||
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Function / homology | ![]() GDF15-GFRAL signaling pathway / negative regulation of growth hormone receptor signaling pathway / response to metformin / reduction of food intake in response to dietary excess / glial cell-derived neurotrophic factor receptor activity / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / posterior midgut development / ureter maturation / embryonic epithelial tube formation ...GDF15-GFRAL signaling pathway / negative regulation of growth hormone receptor signaling pathway / response to metformin / reduction of food intake in response to dietary excess / glial cell-derived neurotrophic factor receptor activity / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / posterior midgut development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Li, J. / Shang, G.J. / Chen, Y.J. / Brautigam, C.A. / Liou, J. / Zhang, X.W. / Bai, X.C. | ||||||
![]() | ![]() Title: Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands. Authors: Jie Li / Guijun Shang / Yu-Ju Chen / Chad A Brautigam / Jen Liou / Xuewu Zhang / Xiao-Chen Bai / ![]() Abstract: RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ...RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ligands but also co-receptors for activation, the mechanisms of which remain unclear due to lack of high-resolution structures of the ligand/co-receptor/receptor complexes. Here, we report cryo-EM structures of the extracellular region ternary complexes of GDF15/GFRAL/RET, GDNF/GFRα1/RET, NRTN/GFRα2/RET and ARTN/GFRα3/RET. These structures reveal that all the four ligand/co-receptor pairs, while using different atomic interactions, induce a specific dimerization mode of RET that is poised to bring the two kinase domains into close proximity for cross-phosphorylation. The NRTN/GFRα2/RET dimeric complex further pack into a tetrameric assembly, which is shown by our cell-based assays to regulate the endocytosis of RET. Our analyses therefore reveal both the common mechanism and diversification in the activation of RET by different ligands. | ||||||
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 324.1 KB | Display | ![]() |
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PDB format | ![]() | 258.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 20572MC ![]() 6q2nC ![]() 6q2oC ![]() 6q2rC ![]() 6q2sC 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
#1: Protein | Mass: 14879.113 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #2: Protein | ![]() Mass: 39120.598 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #3: Protein | Mass: 69100.812 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P07949, ![]() #4: Sugar | ChemComp-NAG / ![]() #5: Chemical | ChemComp-CA / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: RET, GFRAL and GDF15 extracellular complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 200 kDa/nm / Experimental value: NO |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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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![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 15 sec. / Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 |
EM imaging optics | Energyfilter name![]() |
Image scans | Movie frames/image: 30 / Used frames/image: 1-30 |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() ![]() | ||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 520480 / Symmetry type: POINT | ||||||||||||||||||||||||||||||
Atomic model building | B value: 190 / Protocol: FLEXIBLE FIT / Space: REAL |