Crystal structure of TRAF1 TRAF domain and its implications in the TRAF1-mediated intracellular signaling pathway.
Crystal structure of TRAF1 TRAF domain and its implications in the TRAF1-mediated intracellular signaling pathway.
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DOI：
10.1038/srep25526
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发表时间：
2016-05-06
影响因子：
4.6
通讯作者：
Park HH
中科院分区：
文献类型：
--
作者：
Kim CM;Choi JY;Bhat EA;Jeong JH;Son YJ;Kim S;Park HH
肿瘤坏死因子受体相关因子（TRAF）蛋白是含有E3泛素连接酶活性的关键接头分子，在免疫细胞信号传导中起关键作用。TRAF 1是一个缺乏N-末端RING指结构域的TRAF家族。TRAF 1是一种重要的支架蛋白，其通过与TRAF 2直接相互作用作为负或正调节剂参与T细胞中的TNFR 2信号传导，TRAF 2最近被鉴定为神经元细胞死亡中的促凋亡调节剂。在这里，我们报告的第一个晶体结构的TRAF 1 TRAF结构域包含TRAF-N卷曲螺旋结构域和TRAF-C结构域。我们的结构揭示了与其他TRAF家族成员的相似性和差异，这可能是功能相关的TRAF。我们还发现TRAF 1的TRAF-N卷曲螺旋结构域对于蛋白质的三聚体形成和稳定性至关重要。最后，我们发现TRAF 1 TRAF结构域上的保守表面残基可能是与信号分子相互作用的关键结合热点。
TNF-receptor associated factor (TRAF) proteins are key adaptor molecules containing E3 ubiquitin ligase activity that play a critical role in immune cell signaling. TRAF1 is a unique family of TRAF lacking the N-terminal RING finger domain. TRAF1 is an important scaffold protein that participates in TNFR2 signaling in T cells as a negative or positive regulator via direct interaction with TRAF2, which has recently been identified as a pro-apoptotic regulator in neuronal cell death. Here, we report the first crystal structure of the TRAF1 TRAF domain containing both the TRAF-N coiled-coil domain and the TRAF-C domain. Our structure reveals both similarities and differences with other TRAF family members, which may be functionally relevant to TRAFs. We also found that the TRAF-N coiled-coil domain of TRAF1 is critical for the trimer formation and stability of the protein. Finally, we found that conserved surface residues on the TRAF1 TRAF domain that might be binding hot spots that are critical for interaction with signaling molecules.