Updated project metadata. Vaccinia virus immunomodulator A46 is a member of the poxviral Bcl-2-like protein family that inhibits the cellular innate immune response at the level of the TIR domain-containing TLR adaptor proteins MAL, MyD88, TRAM and TRIF. The mechanism of interaction of A46 with its targets has remained unclear. We used BS3 and EDC + sulfo-NHS to cross-link A46 to the TIR domains of MAL and MyD88 to help identify interacting residues and regions.