MDA5:DAK dsRNA:MDA5 Viral dsRNA (-) Stranded dsRNA binds to MDA5 Authored: Garapati, P V, 2010-08-02 Edited: Garapati, P V, 2010-08-02 MDA5 is the closest relative of RIG-I and contains two CARD-like regions, a DExD/H helicase domain, and a C-terminal region similar to the RD of RIG-I. MDA5 with its C-terminal domain (CTD) preferentially binds dsRNA with blunt ends, but does not associate with dsRNA with either 5' or 3' overhangs. Upon binding dsRNA, MDA5 is presumed to undergo structural alteration and, thereby unmask the CARDs enabling them to recruit downstream signal transducer proteins. Dihydroxyacetone kinase (DAK) binds to the CARD domains of MDA5 and acts as a negative regulator of MAD5. It is released upon the conformational change induced by viral RNA binding, allowing the MDA5 CARD domains to bind to IPS-1 CARD. Pubmed17600090 Pubmed18591409 Pubmed19531363 Reactome Database ID Release 43913725 Reactome, http://www.reactome.org ReactomeREACT_25160 Reviewed: Kawai, T, Akira, S, 2010-10-30