TRIF (TICAM1)-mediated TLR4 signaling

TRIF consists of an N-terminal domain (NTD) (1-153), an intermediate disordered proline-rich region, a TIR domain, and a C-terminal region (Mahita J & Sowdhamin R 2017). The disordered proline-rich region between NTD domain and the TIR domain of TICAM1 contains binding sites for TRAF (TNF receptor associated factor) family proteins, which, in turn, recruit protein kinases to promote activation of IRF3 and/or NF-kappa-B (Sato S et al., 2003; Fitzgerald KA et al., 2003). The C-terminal region of TICAM1 (TRIF) can recruit receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and this event is followed by the activation of the IKK complex or the induction of programmed cell death (Han KJ et al., 2004; Kaiser WJ & Offermann MK 2005).