Mendonza Barberá, Elena deCorral-Rodríguez, María AngelesSoares-Schanoski, AlessandraVelarde, MilkoMacieira, SofiaMesserschmidt, AlbrechtLópez Collazo, EduardoFuentes Prior, Pablo2025-02-042025-02-042009-02-270006-291Xhttps://hdl.handle.net/2445/218479Homotypic 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.5 p.application/pdfeng(c) Elsevier B.V., 2009EnzimsFarmacologiaProteïnesEnzymesPharmacologyProteinsinfo:eu-repo/semantics/article7226112025-02-04info:eu-repo/semantics/openAccess