4gl9

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{{STRUCTURE_4gl9| PDB=4gl9 | SCENE= }}
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==Crystal structure of inhibitory protein SOCS3 in complex with JAK2 kinase domain and fragment of GP130 intracellular domain==
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===Crystal structure of inhibitory protein SOCS3 in complex with JAK2 kinase domain and fragment of GP130 intracellular domain===
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<StructureSection load='4gl9' size='340' side='right' caption='[[4gl9]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23454976}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4gl9]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GL9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GL9 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IZA:2-TERT-BUTYL-9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLINE-7-ONE'>IZA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Jak2, mCG_9104 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Il6st ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gl9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gl9 RCSB], [http://www.ebi.ac.uk/pdbsum/4gl9 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The inhibitory protein SOCS3 plays a key part in the immune and hematopoietic systems by regulating signaling induced by specific cytokines. SOCS3 functions by inhibiting the catalytic activity of Janus kinases (JAKs) that initiate signaling within the cell. We determined the crystal structure of a ternary complex between mouse SOCS3, JAK2 (kinase domain) and a fragment of the interleukin-6 receptor beta-chain. The structure shows that SOCS3 binds JAK2 and receptor simultaneously, using two opposing surfaces. While the phosphotyrosine-binding groove on the SOCS3 SH2 domain is occupied by receptor, JAK2 binds in a phosphoindependent manner to a noncanonical surface. The kinase-inhibitory region of SOCS3 occludes the substrate-binding groove on JAK2, and biochemical studies show that it blocks substrate association. These studies reveal that SOCS3 targets specific JAK-cytokine receptor pairs and explains the mechanism and specificity of SOCS action.
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==Function==
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SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition.,Kershaw NJ, Murphy JM, Liau NP, Varghese LN, Laktyushin A, Whitlock EL, Lucet IS, Nicola NA, Babon JJ Nat Struct Mol Biol. 2013 Apr;20(4):469-76. doi: 10.1038/nsmb.2519. Epub 2013 Mar, 3. PMID:23454976<ref>PMID:23454976</ref>
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[[http://www.uniprot.org/uniprot/SOCS3_MOUSE SOCS3_MOUSE]] SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. Probable substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Seems to recognize IL6ST.<ref>PMID:9889194</ref> <ref>PMID:10821852</ref> <ref>PMID:10490101</ref> <ref>PMID:12754505</ref> <ref>PMID:12847520</ref> [[http://www.uniprot.org/uniprot/IL6RB_MOUSE IL6RB_MOUSE]] Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4gl9]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GL9 OCA].
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</div>
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==Reference==
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==See Also==
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<references group="xtra"/><references/>
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*[[Interleukin receptor|Interleukin receptor]]
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*[[Janus kinase|Janus kinase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Non-specific protein-tyrosine kinase]]
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[[Category: Babon, J J.]]
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[[Category: Babon, J J]]
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[[Category: Kershaw, N J.]]
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[[Category: Kershaw, N J]]
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[[Category: Laktyushin, A.]]
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[[Category: Laktyushin, A]]
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[[Category: Murphy, J M.]]
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[[Category: Murphy, J M]]
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[[Category: Nicola, N A.]]
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[[Category: Nicola, N A]]
[[Category: Kinase inhibitor receptor cytokine signalling]]
[[Category: Kinase inhibitor receptor cytokine signalling]]
[[Category: Phosphorylation]]
[[Category: Phosphorylation]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Transferase-transferase inhibitor complex]]

Revision as of 10:53, 21 December 2014

Crystal structure of inhibitory protein SOCS3 in complex with JAK2 kinase domain and fragment of GP130 intracellular domain

4gl9, resolution 3.90Å

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