Cutting edge: Molecular structure of the TLR-associated kinase-4 death domain and its implications for TLR signaling

被引:39
作者
Lasker, MV
Gajjar, MM
Nair, SK
机构
[1] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA
[2] Univ Illinois, Med Scholars Program, Urbana, IL 61801 USA
[3] Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA
关键词
D O I
10.4049/jimmunol.175.7.4175
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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收藏
页码:4175 / 4179
页数:5
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