| First Author | Mendoza-Barberá E | Year | 2009 |
| Journal | Biochem Biophys Res Commun | Volume | 380 |
| Issue | 1 | Pages | 183-7 |
| PubMed ID | 19167362 | Mgi Jnum | J:144963 |
| Mgi Id | MGI:3833023 | Doi | 10.1016/j.bbrc.2009.01.069 |
| Citation | Mendoza-Barbera E, et al. (2009) Contribution of globular death domains and unstructured linkers to MyD88.IRAK-4 heterodimer formation: an explanation for the antagonistic activity of MyD88s. Biochem Biophys Res Commun 380(1):183-7 |
| abstractText | 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 Glu(116) 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. |
