Cutting edge: Molecular structure of the TLR-associated kinase-4 death domain and its implications for TLR signaling
Cutting edge: Molecular structure of the TLR-associated kinase-4 death domain and its implications for TLR signaling
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DOI：
10.4049/jimmunol.175.7.4175
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Nair, SK
中科院分区：
文献类型：
--
作者：
Lasker, MV;Gajjar, MM;Nair, SK
白介素1受体相关蛋白4(IRAK)4是天然免疫的重要组成部分。IRAK-4在小鼠和人中的缺乏导致IL-1和TLR信号的严重损伤。我们已经解决了小鼠肌肉IRAK-4死亡区域的晶体结构，分辨率为1.7埃。这是首次对哺乳动物IRAK家族成员的结构细节一瞥。晶体结构显示了一个带有突出环的六螺旋束，这在IRAK和Pelle中是IRAK-4所独有的，Pelle是果蝇的同源物。这个高度结构化的环包含在螺旋2和3之间，包括11-AA延伸。尽管果蝇和哺乳动物的天然免疫结构域识别被认为非常相似，但这种结构成分指向了巨大的差异。这种结构可以作为未来突变和缺失研究以及潜在药物设计的框架。
IL-1R-associated kinase (IRAK) 4 is an essential component of innate immunity. IRAK-4 deficiency in mice and humans results in severe impairment of IL-1 and TLR signaling. We have solved the crystal structure for the death domain of Mus musculus IRAK-4 to 1.7 angstrom resolution. This is the first glimpse of the structural details of a mammalian IRAK family member. The crystal structure reveals a six-helical bundle with a prominent loop, which among IRAKs and Pelle, a Drosophila homologue, is unique to IRAK-4. This highly structured loop contained between helices two and three, comprises an 11-aa stretch. Although innate immune domain recognition is thought to be very similar between Drosophila and mammals, this structural component points to a drastic difference. This structure can be used as a framework for future mutation and deletion studies and potential drug design.