Structural highlights
3jsv is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Related: | 3f89, 2zvo, 2zvn, 3fx0 |
| Gene: | Ikbkg, Nemo, NEMO(249-343) (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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
NEMO is essential for activation of the NF-kappaB signaling pathway, which is regulated by ubiquitination of proteins. The C-terminal leucine zipper of NEMO and its adjacent coiled-coil region (CC2-LZ) reportedly bind to linear ubiquitin chains with 1 microM affinity and to Lys 63-linked chains with 100 microM affinity. Here we report the crystal structure of the CC2-LZ region of mouse NEMO in complex with Lys 63-linked di-ubiquitin (K63-Ub(2)) at 2.7A resolution. The ubiquitin-binding region consists of a 130A-long helix and forms a parallel coiled-coil dimer. The Ile 44-centered hydrophobic patch of ubiquitin is recognized in the middle of the NEMO ubiquitin-binding region. NEMO interacts with each K63-Ub(2)via a single ubiquitin-binding site, consistent with low affinity binding with K63-Ub(2).
Crystal structure of the NEMO ubiquitin-binding domain in complex with Lys 63-linked di-ubiquitin.,Yoshikawa A, Sato Y, Yamashita M, Mimura H, Yamagata A, Fukai S FEBS Lett. 2009 Oct 20;583(20):3317-22. Epub 2009 Sep 18. PMID:19766637[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Yoshikawa A, Sato Y, Yamashita M, Mimura H, Yamagata A, Fukai S. Crystal structure of the NEMO ubiquitin-binding domain in complex with Lys 63-linked di-ubiquitin. FEBS Lett. 2009 Oct 20;583(20):3317-22. Epub 2009 Sep 18. PMID:19766637 doi:10.1016/j.febslet.2009.09.028
