TRAF4是TRAF家族的独特成员，这对先天免疫反应至关重要，神经系统和其他系统。除了是一种衔接蛋白，在最近的研究中,TRAF4被鉴定为调节蛋白。我们已经通过X射线晶体学方法以2.60µ分辨率确定了TRAF4的TRAF结构域（残基292-466）的晶体结构。三重组装的TRAF4类似于蘑菇形状，包含一个超级螺旋“茎”，由三个右手交织的α螺旋和一个C端“帽”组成，在作为边界的残基L302处划分。类似于其他TRAF，超螺旋“茎”中的分子间疏水相互作用和“帽”区域中的氢键都直接导致TRAF4三聚体的形成。然而,与其他TRAF不同，有一个额外的柔性环（残基421-426），其含有暴露在表面上的先前鉴定的磷酸化位点S426。据报道，该S426被IKKα磷酸化，IKKα是TRAF4-NOD2复合物形成的先决条件，因此可以抑制NOD2诱导的NF-κB激活。因此,TRAF4-TRAF的晶体结构对于理解其特殊功能的分子基础具有重要价值，并为进一步研究提供了结构信息。
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.
