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2zvn

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Revision as of 01:02, 25 December 2014

NEMO CoZi domain incomplex with diubiquitin in P212121 space group

Structural highlights

2zvn is a 8 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2zvo, 3f89
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[NEMO_MOUSE] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Activation of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in immunity, requires binding of NF-kappaB essential modulator (NEMO) to ubiquitinated substrates. Here, we report that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO selectively binds linear (head-to-tail) ubiquitin chains. Crystal structures of the UBAN motif revealed a parallel coiled-coil dimer that formed a heterotetrameric complex with two linear diubiquitin molecules. The UBAN dimer contacted all four ubiquitin moieties, and the integrity of each binding site was required for efficient NF-kappaB activation. Binding occurred via a surface on the proximal ubiquitin moiety and the canonical Ile44 surface on the distal one, thereby providing specificity for linear chain recognition. Residues of NEMO involved in binding linear ubiquitin chains are required for NF-kappaB activation by TNF-alpha and other agonists, providing an explanation for the detrimental effect of NEMO mutations in patients suffering from X-linked ectodermal dysplasia and immunodeficiency.

Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation.,Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I Cell. 2009 Mar 20;136(6):1098-109. PMID:19303852^[2]

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

References

↑ Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, Wallach D, Horwitz MS. Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1042-7. PMID:9927690
↑ Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I. Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation. Cell. 2009 Mar 20;136(6):1098-109. PMID:19303852 doi:10.1016/j.cell.2009.03.007

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2zvn"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2zvn]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZVN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZVN FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zvo|2zvo]], [[3f89|3f89]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zvo|2zvo]], [[3f89|3f89]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zvn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zvn RCSB], [http://www.ebi.ac.uk/pdbsum/2zvn 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=2zvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zvn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2zvn RCSB], [http://www.ebi.ac.uk/pdbsum/2zvn PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/NEMO_MOUSE NEMO_MOUSE]] Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).<ref>PMID:9927690</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 [[Category: Homo sapiens]]
 [[Category: Mus musculus]]
-[[Category: Akutsu, M.]]
+[[Category: Akutsu, M]]
-[[Category: Bloor, S.]]
+[[Category: Bloor, S]]
-[[Category: Dikic, I.]]
+[[Category: Dikic, I]]
-[[Category: Ikeda, F.]]
+[[Category: Ikeda, F]]
-[[Category: Kato, R.]]
+[[Category: Kato, R]]
-[[Category: Kawasaki, M.]]
+[[Category: Kawasaki, M]]
-[[Category: Kensche, T.]]
+[[Category: Kensche, T]]
-[[Category: Komander, D.]]
+[[Category: Komander, D]]
-[[Category: Rahighi, S.]]
+[[Category: Rahighi, S]]
-[[Category: Randow, F.]]
+[[Category: Randow, F]]
-[[Category: Suzuki, N.]]
+[[Category: Suzuki, N]]
-[[Category: Uejima, T.]]
+[[Category: Uejima, T]]
-[[Category: Wakatsuki, S.]]
+[[Category: Wakatsuki, S]]
 [[Category: Metal-binding]]
 [[Category: Nf-kb signaling]]

2zvn

From Proteopedia

Revision as of 01:02, 25 December 2014

NEMO CoZi domain incomplex with diubiquitin in P212121 space group

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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