Cutting edge: Molecular structure of the IL-1R-associated kinase-4 death domain and its implications for TLR signaling

Michael V. Lasker, Mark M. Gajjar, Satish K. Nair

Research output: Contribution to journalArticlepeer-review

Abstract

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 Å 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.

Original languageEnglish (US)
Pages (from-to)4175-4179
Number of pages5
JournalJournal of Immunology
Volume175
Issue number7
DOIs
StatePublished - Oct 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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