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Yorodumi- PDB-8ewy: Structure of Janus Kinase (JAK) dimer complexed with cytokine rec... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ewy | ||||||
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Title | Structure of Janus Kinase (JAK) dimer complexed with cytokine receptor intracellular domain | ||||||
Components |
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Keywords | SIGNALING PROTEIN / JAK / Kinase / Cytokine | ||||||
Function / homology | Function and homology information response to type III interferon / interleukin-28 receptor complex / Interleukin-20 family signaling / mucosal immune response / positive regulation of cellular respiration / protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / positive regulation of homotypic cell-cell adhesion / interleukin-9-mediated signaling pathway ...response to type III interferon / interleukin-28 receptor complex / Interleukin-20 family signaling / mucosal immune response / positive regulation of cellular respiration / protein localization to cell-cell junction / interleukin-11-mediated signaling pathway / CCR5 chemokine receptor binding / positive regulation of homotypic cell-cell adhesion / interleukin-9-mediated signaling pathway / interleukin-4-mediated signaling pathway / interleukin-2-mediated signaling pathway / regulation of defense response to virus by host / interleukin-15-mediated signaling pathway / growth hormone receptor binding / cytokine receptor activity / interleukin-6-mediated signaling pathway / type I interferon-mediated signaling pathway / positive regulation of sprouting angiogenesis / cell surface receptor signaling pathway via JAK-STAT / growth hormone receptor signaling pathway via JAK-STAT / endomembrane system / type II interferon-mediated signaling pathway / extrinsic component of cytoplasmic side of plasma membrane / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / cytokine-mediated signaling pathway / positive regulation of protein localization to nucleus / protein phosphatase binding / defense response to virus / cell differentiation / cytoskeleton / intracellular signal transduction / phosphorylation / response to antibiotic / ubiquitin protein ligase binding / ATP binding / nucleus / cytosol Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 5.5 Å | ||||||
Authors | Caveney, N.A. / Saxton, R.A. / Waghray, D. / Garcia, K.C. | ||||||
Funding support | United States, 1items
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Citation | Journal: Cell Rep / Year: 2023 Title: Structural basis of Janus kinase trans-activation. Authors: Nathanael A Caveney / Robert A Saxton / Deepa Waghray / Caleb R Glassman / Naotaka Tsutsumi / Stevan R Hubbard / K Christopher Garcia / Abstract: Janus kinases (JAKs) mediate signal transduction downstream of cytokine receptors. Cytokine-dependent dimerization is conveyed across the cell membrane to drive JAK dimerization, trans- ...Janus kinases (JAKs) mediate signal transduction downstream of cytokine receptors. Cytokine-dependent dimerization is conveyed across the cell membrane to drive JAK dimerization, trans-phosphorylation, and activation. Activated JAKs in turn phosphorylate receptor intracellular domains (ICDs), resulting in the recruitment, phosphorylation, and activation of signal transducer and activator of transcription (STAT)-family transcription factors. The structural arrangement of a JAK1 dimer complex with IFNλR1 ICD was recently elucidated while bound by stabilizing nanobodies. While this revealed insights into the dimerization-dependent activation of JAKs and the role of oncogenic mutations in this process, the tyrosine kinase (TK) domains were separated by a distance not compatible with the trans-phosphorylation events between the TK domains. Here, we report the cryoelectron microscopy structure of a mouse JAK1 complex in a putative trans-activation state and expand these insights to other physiologically relevant JAK complexes, providing mechanistic insight into the crucial trans-activation step of JAK signaling and allosteric mechanisms of JAK inhibition. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ewy.cif.gz | 315.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ewy.ent.gz | 217.3 KB | Display | PDB format |
PDBx/mmJSON format | 8ewy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ewy_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8ewy_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8ewy_validation.xml.gz | 53.1 KB | Display | |
Data in CIF | 8ewy_validation.cif.gz | 84.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ew/8ewy ftp://data.pdbj.org/pub/pdb/validation_reports/ew/8ewy | HTTPS FTP |
-Related structure data
Related structure data | 28649MC 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
#1: Protein | Mass: 136026.844 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Jak1 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: B1ASP2, non-specific protein-tyrosine kinase #2: Protein | Mass: 9895.373 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Ifnlr1, Il28ra / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q8CGK5 #3: Chemical | #4: Chemical | Has ligand of interest | N | |
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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: Structure of Janus Kinase (JAK) dimer complexed with cytokine receptor intracellular domain Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Trichoplusia ni (cabbage looper) |
Buffer solution | pH: 8 |
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: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: OTHER / Nominal defocus max: 3000 nm / Nominal defocus min: 800 nm |
Image recording | Electron dose: 50.6 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 5.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 174962 / Symmetry type: POINT |