Structural insights into the regulation of MDA5-mediated antiviral signaling activity
EMSL Project ID
50673
Abstract
Effective antiviral immunity involves the recognition of viral dsRNA by the innate immune receptor MDA5 and the subsequent interferon signaling cascade. Aberrant recognition of endogenous “self” RNAs, on the other hand, leads to autoinflammatory disorders. The recognition of “self” RNAs by MDA5 can also be advantageous in the light of recent studies showing its role in anticancer immunotherapy via viral mimicry. The broad implications of MDA5, ranging from viral susceptibility and autoinflammation to cancer immunotherapy, makes it an important pharmacological target. Our recent inhibitor screening studies have helped us in identifying some potential compounds with both strong positive as well as negative impact on MDA5 signaling. In order to understand the mechanistic basis of the activation/inhibition by these compounds we sought to determine high resolution CryoEM structures of MDA5-dsRNA complex bound to these molecules.
Project Details
Start Date
2019-03-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members