Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

Brisse, Morgan; Ly, Hinh

RIG-I (Retinoic acid-inducible gene I) encoded by the DDX58 gene in the human genome (1, 2) and MDA5 (Melanoma Differentiation-Associated protein 5) encoded by the IFIH1 gene (3, 4) are known as important protein initiators of earliest immune responses to viral infection. A relatively large body of work has focused on understanding their roles in triggering the same innate immune pathway as they indeed share many similarities at a structural and functional level. However, it is becoming increasingly clear that there are unique differences between RIG-I and MDA5, such as their activation mechanisms and contextual functionalities, that need to be considered in order to fully appreciate their individual function. A comprehensive analysis of multiple aspects of RIG-I and MDA5 from their evolutionary origins and behavior among different species to their structures and molecular signaling will allow for a more nuanced understanding of their functional purposes.