期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 7, 页码 4175-4179出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.7.4175
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- NINDS NIH HHS [1 F30 NS 048779-01] Funding Source: Medline
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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