Integrative modelling of TIR domain-containing adaptor molecule inducing interferon-β (TRIF) provides insights into its autoinhibited state.

ABSTRACT:

Background

TRIF is a key protein in antiviral innate immunity, operating downstream of TLRs. TRIF activation leads to the production of interferon-β and pro-inflammatory cytokines. There is evidence from experiments to suggest that the N-terminal domain of TRIF binds to its TIR domain to avoid constitutive activation. However, no structure of a complex between the N-terminal domain and the TIR domain exists till date. The disordered nature of the region connecting the N-terminal domain and the TIR domain compounds the issue of elucidating the mechanism of autoinhibition of TRIF. In this study, we have employed an integrative approach consisting of mutual information analysis, docking, molecular dynamics simulations and residue network analysis, in combination with existing experime

SUBMITTER: Mahita J 

PROVIDER: S-EPMC5397763 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature