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Yorodumi- EMDB-28649: Structure of Janus Kinase (JAK) dimer complexed with cytokine rec... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28649 | |||||||||
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Title | Structure of Janus Kinase (JAK) dimer complexed with cytokine receptor intracellular domain | |||||||||
Map data | sharpened map | |||||||||
Sample |
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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 / cytokine receptor activity / growth hormone receptor binding / interleukin-6-mediated signaling pathway / type I interferon-mediated signaling pathway / positive regulation of sprouting angiogenesis / extrinsic component of cytoplasmic side of plasma membrane / cell surface receptor signaling pathway via JAK-STAT / endomembrane system / type II interferon-mediated signaling pathway / 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 / cytoskeleton / intracellular signal transduction / response to antibiotic / ubiquitin protein ligase binding / ATP binding / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 5.5 Å | |||||||||
Authors | Caveney NA / Saxton RA / Waghray D / Garcia KC | |||||||||
Funding support | United States, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28649.map.gz | 4.6 MB | EMDB map data format | |
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Header (meta data) | emd-28649-v30.xml emd-28649.xml | 16.2 KB 16.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28649_fsc.xml | 4.3 KB | Display | FSC data file |
Images | emd_28649.png | 84.6 KB | ||
Masks | emd_28649_msk_1.map | 8.8 MB | Mask map | |
Others | emd_28649_half_map_1.map.gz emd_28649_half_map_2.map.gz | 8.1 MB 8.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28649 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28649 | HTTPS FTP |
-Related structure data
Related structure data | 8ewyMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_28649.map.gz / Format: CCP4 / Size: 8.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 2.21624 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_28649_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_28649_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_28649_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Structure of Janus Kinase (JAK) dimer complexed with cytokine rec...
Entire | Name: Structure of Janus Kinase (JAK) dimer complexed with cytokine receptor intracellular domain |
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Components |
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-Supramolecule #1: Structure of Janus Kinase (JAK) dimer complexed with cytokine rec...
Supramolecule | Name: Structure of Janus Kinase (JAK) dimer complexed with cytokine receptor intracellular domain type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-Macromolecule #1: Tyrosine-protein kinase
Macromolecule | Name: Tyrosine-protein kinase / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: non-specific protein-tyrosine kinase |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 136.026844 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MQYLNIKEDC NAMAFCAKMR SFKKTEVKQV VPEPGVEVTF YLLDREPLRL GSGEYTAEEL CIRAAQECSI SPLCHNLFAL YDESTKLWY APNRIITVDD KTSLRLHYRM RFYFTNWHGT NDNEQSVWRH SPKKQKNGYE KKRVPEATPL LDASSLEYLF A QGQYDLIK ...String: MQYLNIKEDC NAMAFCAKMR SFKKTEVKQV VPEPGVEVTF YLLDREPLRL GSGEYTAEEL CIRAAQECSI SPLCHNLFAL YDESTKLWY APNRIITVDD KTSLRLHYRM RFYFTNWHGT NDNEQSVWRH SPKKQKNGYE KKRVPEATPL LDASSLEYLF A QGQYDLIK CLAPIRDPKT EQDGHDIENE CLGMAVLAIS HYAMMKKMQL PELPKDISYK RYIPETLNKS IRQRNLLTRM RI NNVFKDF LKEFNNKTIC DSSVSTHDLK VKYLATLETL TKHYGAEIFE TSMLLISSEN ELSRCHSNDS GNVLYEVMVT GNL GIQWRQ KPNVVPVEKE KNKLKRKKLE YNKHKKDDER NKLREEWNNF SYFPEITHIV IKESVVSINK QDNKNMELKL SSRE EALSF VSLVDGYFRL TADAHHYLCT DVAPPLIVHN IQNGCHGPIC TEYAINKLRQ EGSEEGMYVL RWSCTDFDNI LMTVT CFEK SEVLGGQKQF KNFQIEVQKG RYSLHGSMDH FPSLRDLMNH LKKQILRTDN ISFVLKRCCQ PKPREISNLL VATKKA QEW QPVYSMSQLS FDRILKKDII QGEHLGRGTR THIYSGTLLD YKDEEGIAEE KKIKVILKVL DPSHRDISLA FFEAASM MR QVSHKHIVYL YGVCFRDVEN IMVEEFVEGG PLDLFMHRKS DALTTPWKFK VAKQLASALS YLEDKDLVHG NVCTKNLL L AREGIDSDIG PFIKLSDPGI PVSVLTRQEC IERIPWIAPE CVEDSKNLSV AADKWSFGTT LWEICYNGEI PLKDKTLIE KERFYESRCR PVTPSCKELA DLMTRCMNYD PNQRPFFRAI MRDINKLEEQ NPDIVSEKQP TTEVDPTHFE KRFLKRIRDL GEGHFGKVE LCRYDPEGDN TGEQVAVKSL KPESGGNHIA DLKKEIEILR NLYHENIVKY KGICMEDGGN GIKLIMEFLP S GSLKEYLP KNKNKINLKQ QLKYAIQICK GMDYLGSRQY VHRDLAARNV LVESEHQVKI GDFGLTKAIE TDKEYYTVKD DR DSPVFWY APECLIQCKF YIASDVWSFG VTLHELLTYC DSDFSPMALF LKMIGPTHGQ MTVTRLVNTL KEGKRLPCPP NCP DEVYQL MRKCWEFQPS NRTTFQNLIE GFEALLKGSD RKAAVSHWQH HHHHHHH |
-Macromolecule #2: Interferon lambda receptor 1
Macromolecule | Name: Interferon lambda receptor 1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 9.895373 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: GPRMKQLEDK VEELLSKNYH LENEVARLKK LVGERKIMKG NPWFQGVKTP RALDFSEYRY PVATFQPSGP EFSDDLILCP QKELT |
-Macromolecule #3: ADENOSINE
Macromolecule | Name: ADENOSINE / type: ligand / ID: 3 / Number of copies: 2 / Formula: ADN |
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Molecular weight | Theoretical: 267.241 Da |
Chemical component information | ChemComp-ADN: |
-Macromolecule #4: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: ADP |
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Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ChemComp-ADP: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.6 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: OTHER / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |