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4d0p

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Revision as of 18:21, 4 August 2016

Crystal structure of human CSN4

Structural highlights

4d0p is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CSN4_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. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, 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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Ubiquitination is a crucial cellular signalling process, and is controlled on multiple levels. Cullin-RING E3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). CSN inactivates CRLs by removing their covalently attached activator, NEDD8. NEDD8 cleavage by CSN is catalysed by CSN5, a Zn2+-dependent isopeptidase that is inactive in isolation. Here we present the crystal structure of the entire approximately 350-kDa human CSN holoenzyme at 3.8 A resolution, detailing the molecular architecture of the complex. CSN has two organizational centres: a horseshoe-shaped ring created by its six proteasome lid-CSN-initiation factor 3 (PCI) domain proteins, and a large bundle formed by the carboxy-terminal alpha-helices of every subunit. CSN5 and its dimerization partner, CSN6, are intricately embedded at the core of the helical bundle. In the substrate-free holoenzyme, CSN5 is autoinhibited, which precludes access to the active site. We find that neddylated CRL binding to CSN is sensed by CSN4, and communicated to CSN5 with the assistance of CSN6, resulting in activation of the deneddylase.

Crystal structure of the human COP9 signalosome.,Lingaraju GM, Bunker RD, Cavadini S, Hess D, Hassiepen U, Renatus M, Fischer ES, Thoma NH Nature. 2014 Jul 16. doi: 10.1038/nature13566. PMID:25043011^[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
↑ Granata A, Koo SJ, Haucke V, Schiavo G, Warner TT. CSN complex controls the stability of selected synaptic proteins via a torsinA-dependent process. EMBO J. 2011 Jan 5;30(1):181-93. doi: 10.1038/emboj.2010.285. Epub 2010 Nov 19. PMID:21102408 doi:http://dx.doi.org/10.1038/emboj.2010.285
↑ Lingaraju GM, Bunker RD, Cavadini S, Hess D, Hassiepen U, Renatus M, Fischer ES, Thoma NH. Crystal structure of the human COP9 signalosome. Nature. 2014 Jul 16. doi: 10.1038/nature13566. PMID:25043011 doi:http://dx.doi.org/10.1038/nature13566

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/4d0p"

Categories: Bunker, R D | Lingaraju, G M | Thoma, N H | Pci | Signaling protein

@@ Line 1: / Line 1: @@
 ==Crystal structure of human CSN4==
 <StructureSection load='4d0p' size='340' side='right' caption='[[4d0p]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4d0p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4D0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4D0P FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=4d0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0p OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4d0p RCSB], [http://www.ebi.ac.uk/pdbsum/4d0p PDBsum]</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=4d0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4d0p OCA], [http://pdbe.org/4d0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4d0p RCSB], [http://www.ebi.ac.uk/pdbsum/4d0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4d0p ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4d0p" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Signalosome|Signalosome]]
 == References ==
 <references/>

4d0p

From Proteopedia

Revision as of 18:21, 4 August 2016

Crystal structure of human CSN4

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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