2jz3

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==SOCS box elonginBC ternary complex==
==SOCS box elonginBC ternary complex==
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<StructureSection load='2jz3' size='340' side='right'caption='[[2jz3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2jz3' size='340' side='right'caption='[[2jz3]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2jz3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JZ3 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2jz3]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JZ3 FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jz3 OCA], [https://pdbe.org/2jz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jz3 RCSB], [https://www.ebi.ac.uk/pdbsum/2jz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jz3 ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jz3 OCA], [https://pdbe.org/2jz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jz3 RCSB], [https://www.ebi.ac.uk/pdbsum/2jz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jz3 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://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> [[https://www.uniprot.org/uniprot/ELOC_MOUSE ELOC_MOUSE]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. [[https://www.uniprot.org/uniprot/ELOB_HUMAN ELOB_HUMAN]] SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).<ref>PMID:7638163</ref> <ref>PMID:15590694</ref> The elongin BC complex seems to be involved as an adapter protein in the proteasomal degradation of target proteins via different E3 ubiquitin ligase complexes, including the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes.<ref>PMID:7638163</ref> <ref>PMID:15590694</ref>
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[https://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>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jz3 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jz3 ConSurf].
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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Suppressor of cytokine signalling 3 (SOCS3) is responsible for regulating the cellular response to a variety of cytokines, including interleukin 6 and leukaemia inhibitory factor. Identification of the SOCS box domain led to the hypothesis that SOCS3 can associate with functional E3 ubiquitin ligases and thereby induce the degradation of bound signalling proteins. This model relies upon an interaction between the SOCS box, elonginBC and a cullin protein that forms the E3 ligase scaffold. We have investigated this interaction in vitro using purified components and show that SOCS3 binds to elonginBC and cullin5 with high affinity. The SOCS3-elonginBC interaction was further characterised by determining the solution structure of the SOCS box-elonginBC ternary complex and by deletion and alanine scanning mutagenesis of the SOCS box. These studies revealed that conformational flexibility is a key feature of the SOCS-elonginBC interaction. In particular, the SOCS box is disordered in isolation and only becomes structured upon elonginBC association. The interaction depends upon the first 12 residues of the SOCS box domain and particularly on a deeply buried, conserved leucine. The SOCS box, when bound to elonginBC, binds tightly to cullin5 with 100 nM affinity. Domains upstream of the SOCS box are not required for elonginBC or cullin5 association, indicating that the SOCS box acts as an independent binding domain capable of recruiting elonginBC and cullin5 to promote E3 ligase formation.
 
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The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase.,Babon JJ, Sabo JK, Soetopo A, Yao S, Bailey MF, Zhang JG, Nicola NA, Norton RS J Mol Biol. 2008 Sep 12;381(4):928-40. Epub 2008 Jun 20. PMID:18590740<ref>PMID:18590740</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 2jz3" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Mus musculus]]
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[[Category: Babon, J J]]
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[[Category: Babon JJ]]
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[[Category: Bailey, M F]]
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[[Category: Bailey MF]]
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[[Category: Nicola, N A]]
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[[Category: Nicola NA]]
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[[Category: Norton, R S]]
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[[Category: Norton RS]]
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[[Category: Sabo, J]]
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[[Category: Sabo J]]
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[[Category: Soetopo, A]]
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[[Category: Soetopo A]]
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[[Category: Yao, S]]
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[[Category: Yao S]]
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[[Category: Zhang, J]]
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[[Category: Zhang J]]
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[[Category: Cytokine signaling]]
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[[Category: Elongin]]
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[[Category: Growth regulation]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Sh2 domain]]
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[[Category: Signal transduction inhibitor]]
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[[Category: Signaling protein]]
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[[Category: Socs protein]]
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[[Category: Transcription]]
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[[Category: Transcription inhibitor-transcription complex]]
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[[Category: Transcription regulation]]
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[[Category: Ubl conjugation pathway]]
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Current revision

SOCS box elonginBC ternary complex

PDB ID 2jz3

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