4qft

From Proteopedia

(Difference between revisions)

Revision as of 11:28, 15 February 2023

Structure of COP9 signalosome complex subunit 6

Structural highlights

4qft is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSN6_HUMAN Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Stabilizes RFWD2/COP1 through reducing RFWD2 auto-ubiquitination and decelerating RFWD2 turnover rate, hence regulates the ubiquitination of RFWD2 targets.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

The Cop9 signalosome complex (CSN) regulates the functional cycle of the major E3 ubiquitin ligase family, the cullin RING E3 ubiquitin ligases (CRLs). Activated CRLs are covalently modified by the ubiquitin-like protein Nedd8 (neural precursor cell expressed developmentally down-regulated protein 8). CSN serves an essential role in myriad cellular processes by reversing this modification through the isopeptidase activity of its CSN5 subunit. CSN5 alone is inactive due to an auto-inhibited conformation of its catalytic domain. Here we report the molecular basis of CSN5 catalytic domain activation and unravel a molecular hierarchy in CSN deneddylation activity. The association of CSN5 and CSN6 MPN (for Mpr1/Pad1 N-terminal) domains activates its isopeptidase activity. The CSN5/CSN6 module, however, is inefficient in CRL deneddylation, indicating a requirement of further elements in this reaction such as other CSN subunits. A hybrid molecular model of CSN5/CSN6 provides a structural framework to explain these functional observations. Docking this model into a published CSN electron density map and using distance constraints obtained from cross-linking coupled to mass-spectrometry, we find that the C-termini of the CSN subunits could form a helical bundle in the centre of the structure. They likely play a key scaffolding role in the spatial organization of CSN and precise positioning of the dimeric MPN catalytic core.

Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer.,Birol M, Enchev RI, Padilla A, Stengel F, Aebersold R, Betzi S, Yang Y, Hoh F, Peter M, Dumas C, Echalier A PLoS One. 2014 Aug 21;9(8):e105688. doi: 10.1371/journal.pone.0105688., eCollection 2014. PMID:25144743^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469-78. PMID:9535219
↑ Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. EMBO J. 2001 Apr 2;20(7):1630-9. PMID:11285227 doi:http://dx.doi.org/10.1093/emboj/20.7.1630
↑ Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome. Science. 2001 May 18;292(5520):1382-5. Epub 2001 May 3. PMID:11337588 doi:http://dx.doi.org/10.1126/science.1059780
↑ Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y. The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell. 2003 May 2;113(3):357-67. PMID:12732143
↑ Uhle S, Medalia O, Waldron R, Dumdey R, Henklein P, Bech-Otschir D, Huang X, Berse M, Sperling J, Schade R, Dubiel W. Protein kinase CK2 and protein kinase D are associated with the COP9 signalosome. EMBO J. 2003 Mar 17;22(6):1302-12. PMID:12628923 doi:http://dx.doi.org/10.1093/emboj/cdg127
↑ Choi HH, Gully C, Su CH, Velazquez-Torres G, Chou PC, Tseng C, Zhao R, Phan L, Shaiken T, Chen J, Yeung SC, Lee MH. COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3sigma. Oncogene. 2011 Dec 1;30(48):4791-801. doi: 10.1038/onc.2011.192. Epub 2011 May, 30. PMID:21625211 doi:http://dx.doi.org/10.1038/onc.2011.192
↑ Birol M, Enchev RI, Padilla A, Stengel F, Aebersold R, Betzi S, Yang Y, Hoh F, Peter M, Dumas C, Echalier A. Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer. PLoS One. 2014 Aug 21;9(8):e105688. doi: 10.1371/journal.pone.0105688., eCollection 2014. PMID:25144743 doi:http://dx.doi.org/10.1371/journal.pone.0105688

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qft"

@@ Line 3: / Line 3: @@
 <StructureSection load='4qft' size='340' side='right'caption='[[4qft]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4qft]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QFT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QFT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4qft]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QFT FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">COPS6, CSN6, HVIP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</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=4qft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qft OCA], [https://pdbe.org/4qft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qft RCSB], [https://www.ebi.ac.uk/pdbsum/4qft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qft ProSAT]</span></td></tr>
-<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=4qft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qft OCA], [http://pdbe.org/4qft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qft RCSB], [http://www.ebi.ac.uk/pdbsum/4qft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qft ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CSN6_HUMAN CSN6_HUMAN]] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Stabilizes RFWD2/COP1 through reducing RFWD2 auto-ubiquitination and decelerating RFWD2 turnover rate, hence regulates the ubiquitination of RFWD2 targets.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> <ref>PMID:21625211</ref>
+[https://www.uniprot.org/uniprot/CSN6_HUMAN CSN6_HUMAN] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Stabilizes RFWD2/COP1 through reducing RFWD2 auto-ubiquitination and decelerating RFWD2 turnover rate, hence regulates the ubiquitination of RFWD2 targets.<ref>PMID:9535219</ref> <ref>PMID:11285227</ref> <ref>PMID:11337588</ref> <ref>PMID:12732143</ref> <ref>PMID:12628923</ref> <ref>PMID:21625211</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Birol, M]]
+[[Category: Birol M]]
-[[Category: Dumas, C]]
+[[Category: Dumas C]]
-[[Category: Echalier, A]]
+[[Category: Echalier A]]
-[[Category: Hoh, F]]
+[[Category: Hoh F]]
-[[Category: Signaling protein]]
-[[Category: Subunit of the cop9 signalosome]]

4qft

From Proteopedia

Revision as of 11:28, 15 February 2023

Structure of COP9 signalosome complex subunit 6

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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