Cutting Edge: Molecular Structure of the IL-1R-Associated Kinase-4 Death Domain and Its Implications for TLR Signaling

Journal Article · Mon Jul 19 00:00:00 EDT 2010 · J. Immunol.

OSTI ID:1008576

Lasker, Michael V; Gajjar, Mark M; Nair, Satish K ^[1]

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1. UIUC

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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1008576
• Journal Information: J. Immunol., Vol. 175, Issue (1) ; 10, 2005; ISSN 0022-1767
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
CRYSTAL STRUCTURE
DEATH
DESIGN
DROSOPHILA
IMMUNITY
MAMMALS
MICE
MOLECULAR STRUCTURE
MUTATIONS
PHOSPHOTRANSFERASES
RESOLUTION