HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lasker, M. V. Articles by Nair, S. K. Search for Related Content PubMed PubMed Citation Articles by Lasker, M. V. Articles by Nair, S. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein Structure UniGene

Cutting Edge: Molecular Structure of the IL-1R-Associated Kinase-4 Death Domain and Its Implications for TLR Signaling¹

Michael V. Lasker^*,, Mark M. Gajjar^* and Satish K. Nair^2,*,

^* Department of Biochemistry, Medical Scholars Program, and Center for Biophysics and Computational Biology, University of Illinois, Urbana-Champaign, Urbana, IL 61801

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.

This article has been cited by other articles:

				A. Kuglstatter, A. G. Villasenor, D. Shaw, S. W. Lee, S. Tsing, L. Niu, K. W. Song, J. W. Barnett, and M. F. Browner Cutting Edge: IL-1 Receptor-Associated Kinase 4 Structures Reveal Novel Features and Multiple Conformations J. Immunol., March 1, 2007; 178(5): 2641 - 2645. [Abstract] [Full Text] [PDF]

				S. M. Miggin and L. A. J. O'Neill New insights into the regulation of TLR signaling J. Leukoc. Biol., August 1, 2006; 80(2): 220 - 226. [Abstract] [Full Text] [PDF]

				M. V. Lasker and S. K. Nair Intracellular TLR Signaling: A Structural Perspective on Human Disease J. Immunol., July 1, 2006; 177(1): 11 - 16. [Abstract] [Full Text] [PDF]

				M. V. Lasker, S. M. Kuruvilla, M. M. Gajjar, A. Kapoor, and S. K. Nair Metal Ion-Mediated Reduction in Surface Entropy Improves Diffraction Quality of Crystals of the IRAK-4 Death Domain. J. Biomol. Tech., April 1, 2006; 17(2): 114 - 121. [Abstract] [Full Text] [PDF]