We are studying the helicases mda5, RIG-I and LGP2 that are involved in the innate immune response to viral infection. These proteins detect dsRNA or 5‘ppp-ssRNA that then leads to exposure of two N-terminal CARD domains. These interact with the N-terminal CARD domain of the adaptor protein IPS1 (aka VISA, CARDIF, MAVIS), a protein linked to the mitochondrial membrane. This interaction then promotes the recruitment of kinases that lead to the phosphorylation of transcription factors, and ultimately the expression of interferon. This is a collaboration with Rick Randall at St Andrews.

We have determine the structure of the IPS-1 CARD domain as an MBP-fusion protein.