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, TKFC) 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).
Strong, RK, Xu, H, Lu, C, Li, X, Stewart, M, Li, P, Igumenova, T
Hiiragi, A, Kawai, T, Mikamo-Satoh, E, Takeuchi, O, Fujita, T, Matsushita, K, Akira, S, Hirai, R, Dermody, TS, Kato, H
Zhang, Y, Li, S, Tien, P, Chen, D, Xu, LG, Zhang, M, Tian, Y, Diao, F, Shu, HB, Zhong, B, Zhai, Z, Wang, RP
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