J Biol Chem. 2009 Sep 11;284(37):25404-11. Epub 2009 Jul 10.

An oligomeric signaling platform formed by the Toll-like receptor signal transducers MyD88 and IRAK-4.External

Motshwene, P. G., Moncrieffe, M. C., Grossmann, J. G., Kao, C., Ayaluru, M., Sandercock, A. M., Robinson, C. V., Latz, E., Gay, N. J.,
--- - Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Toll-like receptors (TLRs) mediate responses to pathogen-associated molecules as part of the vertebrate innate immune response to infection. Receptor dimerization is coupled to downstream signal transduction by the recruitment of a post-receptor complex containing the adaptor protein MyD88 and the IRAK protein kinases. In this work, we show that the death domains of human MyD88 and IRAK-4 assemble into closed complexes having unusual stoichiometries of 7:4 and 8:4, the Myddosome. Formation of the Myddosome is likely to be a key event for TLR4 signaling in vivo as we show here that pathway activation requires that the receptors cluster into lipid rafts. Taken together, these findings indicate that TLR activation causes the formation of a highly oligomeric signaling platform analogous to the death-inducing signaling complex of the Fas receptor pathway.
PMID: 19592493External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD IRAK4 Link Myd88 In vitro purification protein assembly(chemical crosslinking) Human 1-152 E.coli Human 1-110 E.coli 19592493
DD IRAK4 Link Myd88 In vitro purification protein assembly(Size-exclusion chromatography) Human 1-152 E.coli Human 1-110 E.coli 19592493
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
DD IRAK4 Link Myd88 Gel filtration 4:7, 4:8 19592493
DD IRAK4 Link Myd88 Gel filtration 7:4, 8:4 19592493
(Link: click this icon to show interactions only between the two corresponding DDs)