3a9k

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Crystal structure of the mouse TAB3-NZF in complex with Lys63-linked di-ubiquitinCrystal structure of the mouse TAB3-NZF in complex with Lys63-linked di-ubiquitin

Structural highlights

3a9k is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:Ubiquitin (LK3 transgenic mice), TAB3 (AMINO ACIDS 688 - 716) (LK3 transgenic mice)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TAB3_MOUSE] Adapter linking MAP3K7/TAK1 and TRAF6 or TRAF2. Mediator of MAP3K7 activation, respectively in the IL-1 and TNF signaling pathways. Plays a role in activation of NF-kappa-B and AP1 transcription factor (By similarity).

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

TAB2 and TAB3 activate the Jun N-terminal kinase and nuclear factor-kappaB pathways through the specific recognition of Lys 63-linked polyubiquitin chains by its Npl4 zinc-finger (NZF) domain. Here we report crystal structures of the TAB2 and TAB3 NZF domains in complex with Lys 63-linked diubiquitin at 1.18 and 1.40 A resolutions, respectively. Both NZF domains bind to the distal ubiquitin through a conserved Thr-Phe dipeptide that has been shown to be important for the interaction of the NZF domain of Npl4 with monoubiquitin. In contrast, a surface specific to TAB2 and TAB3 binds the proximal ubiquitin. Both the distal and proximal binding sites of the TAB2 and TAB3 NZF domains recognize the Ile 44-centred hydrophobic patch on ubiquitin but do not interact with the Lys 63-linked isopeptide bond. Mutagenesis experiments show that both binding sites are required to enable binding of Lys 63-linked diubiquitin. We therefore propose a mechanism for the recognition of Lys 63-linked polyubiquitin chains by TAB2 and TAB3 NZF domains in which diubiquitin units are specifically recognized by a single NZF domain.

Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3.,Sato Y, Yoshikawa A, Yamashita M, Yamagata A, Fukai S EMBO J. 2009 Dec 16;28(24):3903-9. Epub . PMID:19927120[1]

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

See Also

References

  1. Sato Y, Yoshikawa A, Yamashita M, Yamagata A, Fukai S. Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3. EMBO J. 2009 Dec 16;28(24):3903-9. Epub . PMID:19927120 doi:10.1038/emboj.2009.345

3a9k, resolution 1.40Å

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