Interferon-induced helicase C domain-containing protein 1 (IFIH1, MDA5) is the closest relative of Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I). It contains two Caspase activation and recruitment domain (CARD)-like regions, a DExD/H helicase domain, and a C-terminal region similar to the RD of DDX58. IFIH1, via its C-terminal domain (CTD), preferentially binds dsRNA with blunt ends. It does not associate with dsRNA having 5' or 3' overhangs. Upon binding dsRNA, IFIH1 is presumed to undergo a structural alteration that unmasks the CARDs enabling them to recruit downstream signal transducer proteins. Dihydroxyacetone kinase (DAK) binds to the CARD domains of IFIH1, acting as a negative regulator. It is released upon the conformational change induced by viral RNA binding, allowing the CARD domains to bind to the CARD of Mitochondrial antiviral-signaling protein (MAVS, IPS-1).