Biochem Biophys Res Commun. 2007 Mar 23;354(4):1089-94. Epub 2007 Jan 26.

The death domain of IRAK-1: an oligomerization domain mediating interactions with MyD88, Tollip, IRAK-1, and IRAK-4.External

Neumann, D., Kollewe, C., Resch, K., Martin, M. U.,
--- - Department for Pharmacology, Hannover Medical School, Carl-Neuberg-Str 1, D-30623 Hannover, Germany. neumann.detlef@mh-hannover.de
Ligand binding in the Toll-like/interleukin-1 receptor family results in the recruitment of an intracellular signaling complex. IRAK-1, which is centrally involved in this complex, is able to homo-oligomerize and to bind to Tollip and the adapters MyD88 and IRAK-4. The interactions of IRAK-1 with MyD88 or Tollip are mediated by the N-terminal part of IRAK-1, containing the death domain with the highly conserved threonine at position 66 (T66). Mutation of this amino acid into alanine or aspartic acid stabilized binding to MyD88, Tollip, and IRAK-4, allowing the definitive experimental proof, that all these interactions are mediated by the death domain of IRAK-1. Homo-oligomerization of IRAK-1, which is mediated by the death domain too, is not affected by mutation of T66. Finally, mutation of IRAK-1 at T66 not only allowed stable binding to the signaling adapters, but also enhanced its signaling capacity.
PMID: 17276401External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD IRAK1 Link IRAK1 Co-immunoprecipitation HEK293 Human Full length Human 2-109 17276401
DD IRAK1 Link IRAK4 Co-immunoprecipitation HEK293 Human Full length Not specified Not specified 17276401
DD IRAK1 Link IRAK4 Co-immunoprecipitation HEK293 Human 2-109 Not specified Not specified 17276401
DD IRAK1 Link Myd88 Co-immunoprecipitation HEK293 Human Full length Not specified Not specified 17276401
DD IRAK1 Link Myd88 Co-immunoprecipitation HEK293 Human 2-109 Not specified Not specified 17276401
(Link: click this icon to show interactions only between the two corresponding DDs)