Structural biology study of human TNF receptor associated factor 4 TRAF domain.
TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to be an adaptor protein, TRAF4 was identified as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 Å resolution by X-ray crystallography method. The trimericly assembled TRAF4 resembles a mushroom shape, containing a super helical "stalk" which is made of three right-handed intertwined α helixes and a C-terminal "cap", which is divided at residue L302 as a boundary. Similar to other TRAFs, both intermolecular hydrophobic interaction in super helical "stalk" and hydrogen bonds in "cap" regions contribute directly to the formation of TRAF4 trimer. However, differing from other TRAFs, there is an additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface. This S426 was reported to be phosphorylated by IKKα which is the pre-requisite for TRAF4-NOD2 complex formation and thus to inhibit NOD2-induced NF-κB activation. Therefore, the crystal structure of TRAF4-TRAF is valuable for understanding its molecular basis for its special function and provides structural information for further studies.
['Niu|Fengfeng|F|', 'Ru|Heng|H|', 'Ding|Wei|W|', 'Ouyang|Songying|S|', 'Liu|Zhi-Jie|ZJ|']
D000595:Amino Acid Sequence D001665:Binding Sites D018360:Crystallography, X-Ray D006801:Humans D057927:Hydrophobic and Hydrophilic Interactions D008958:Models, Molecular D010766:Phosphorylation D000072756:Protein Conformation, alpha-Helical D000072417:Protein Domains D020836:Protein Structure, Quaternary D011994:Recombinant Proteins D017386:Sequence Homology, Amino Acid D053449:TNF Receptor-Associated Factor 4
TRAF domain TRAF4 crystal structure phosphorylation site additional loop