کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1933966 | 1050630 | 2009 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Contribution of globular death domains and unstructured linkers to MyD88·IRAK-4 heterodimer formation: An explanation for the antagonistic activity of MyD88s Contribution of globular death domains and unstructured linkers to MyD88·IRAK-4 heterodimer formation: An explanation for the antagonistic activity of MyD88s](/preview/png/1933966.png)
Homotypic interactions of death domains (DD) mediate complex formation between MyD88 and IL-1 receptor-associated kinases (IRAKs). A truncated splice variant of MyD88, MyD88s, cannot recruit IRAK-4 and fails to elicit inflammatory responses. We have generated recombinant DD of MyD88 and IRAK-4, both alone and extended by the linkers to TIR or kinase domains. We show that both MyD88 DD variants bind to the linker-extended IRAK-4 DD and pull-down full-length IRAK-4 from monocyte extracts. By contrast, residues up to Glu116 from the DD–kinase connector of IRAK-4 are needed for strong interactions with the adaptor. Our findings indicate that residues 110–120, which form a C-terminal extra helix in MyD88, but not the irregular linker between DD and TIR domains, are required for IRAK-4 recruitment, and provide a straightforward explanation for the negative regulation of innate immune responses mediated by MyD88s.
Journal: Biochemical and Biophysical Research Communications - Volume 380, Issue 1, 27 February 2009, Pages 183–187