FIG 9.

Proposed model for the role of ADAP2 in antiviral response. A cartoon showing the proposed model to explain the mode of action of ADAP2 during RIG-I signaling. The proteins are shown with their domains labeled. The interactions of ADAP2 with individual protein are specifically marked at their experimentally identified sites of interaction, except for TRAF3. (A) In uninfected cells, ADAP2 is not in complex with any other protein of PRR signaling pathway. (B) Upon viral infection, two independent events will happen: (i) sensing of virus by RIG-I activates and induces polymerization of MAVS, and (ii) ADAP2 forms a complex with TRAF3, NEMO, TBK1 and IRF3, triggered by signal-1. This will bring IRF3 in proximity to TBK1. (C) In the later stages of viral infection, ADAP2-NEMO-TBK1-IRF3 complex will bind to polymerized MAVS, likely triggered by an unidentified signal-2. This will activate TBK1 to phosphorylate IRF3. KBD, kinase binding domain; KD, kinase domain; CC, coiled coil; ULD, ubiquitin like domain; IAD, IRF association domain; DBD, DNA binding domain; CARD, caspase activation and recruitment domain.