• YAKHAK HOEJI
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• v.47 no.3
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• pp.180-183
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• 2003

Crystal structure of TRAF6 in complex with TRAF6-binding sites from CD40 was previously determined. The structure revealed a distinct TRAF6-binding groove of CD40, the key structural determinant of interaction. The structural information leads to a proposed TRAF6-binding motif. This allows the identification of TRAF6-binding sequences in the hIRAK protein, whose functional requirement in IL-1/Toll-like receptor superfamilies-mediated signal transduction is further demonstrated using site-directed mutagenesis. The mutational effects of hIRAK on the down-stream NF-kB signaling shows the importance of the TRAF6 interface for signaling by IL-1/Toll-like receptor superfamilies.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.311.1-311.1
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• 2002

Crystal structure of TRAF6 in complex with TRAF6-binding sites from CD40 was previously determined. The structure revealed a distinct TRAF6-binding groove of CD40. the key structural determinant of interaction. The structural information leads to a proposed TRAF6-binding motif. This allows the identification of TRAF6-binding sequences in the hlRAK protein, whose functional requirement in IL-1 mediated signal transduction is further demonstrated using site-directed mutagenesis. The mutational in IL-1 mediated signal transduction is further dimonstrated using site-directed mutagenesis. The mutational effects of hlRAK on the down-stream NF-${\kappa}$ signaling shows the importance of the TRAF6 interface for signaling by IL-1.

• Journal of Microbiology
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• v.37 no.4
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• pp.256-262
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• 1999

Latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) is an integral membrane protein with six transmembrane domains, which is essential for EBV-induced B cell transformation. LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR) like membrane receptor, whose signaling requires recruitment of TNFR-associated factors (TRAFs) and leads to NF-${\kappa}B$ activation. NF-${\kappa}B$ activation by LMP1 is critical for B cell transformation and has been linked to many phenotypic changes associated with EBV-induced B cell transformation. Deletion analysis has identified two NF-${\kappa}B$ activation regions in the carboxy terminal cytoplasmic domains of LMP1, termed CTAR1 (residues 194-232) and CTAR2 (351-386). The membrane proximal C-terminal domain was precisely mapped to a PXQXT motif (residues 204-208) involved in TRAF binding as well as NF-${\kappa}B$ activation. In this study, we dissected the CTAR2 region, which is the major NF-${\kappa}B$ signaling effector of LMP1, to determine a minimal functional sequence. A series of LMP1 mutant constructs systematically deleted for the CTAR2 region were prepared, and NF-${\kappa}B$ activation activity of these mutants were assessed by transiently expressing them in 293 cells and Jurkat T cells. The NF-${\kappa}B$ activation domain of CTAR2 appears to reside in a stretch of 6 amino acids (residues 379-384) at the end of the carboxy terminus.