Structural biology study of human TNF receptor associated factor 4 TRAF domain

Abstract

TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to being an adaptor protein, TRAF4 was identifi ed as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 ? 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.

Keywords

TRAF4 / TRAF domain / crystal structure / additional loop / phosphorylation site

References

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