This family of proteins represents the regulatory domain RD of RIG-I, a protein which initiates a signalling cascade that provides essential antiviral protection for the host. The RD domain binds viral RNA, activating the RIG-I ATPase by RNA-dependant dimerisation. The structure of RD contains a zinc-binding domain and is thought to confer ligand specificity .
Intracellular RIG-I-like receptors (RLRs: retinoic acid-inducible gene I, RIG-I; melanoma differenciation-associated gene 5, MDA-5; and laboratory of genetics and physiology 2, LGP2) recognize viral RNAs as pathogen-associated molecular patterns (PAMPs) and initiate an antiviral immune response. RLRs belong to the superfamily 2 (SF2) helicases or ATPases. Among SF2 ATPases, RIG-I, MDA5, and LGP2 possess a unique domain structure. RIG-I and MDA5 consist of two N-terminal caspase activation and recruitment domains (CARDs), a central SF2 type DECH box ATPase domain (consisting of two RecA-like helicase domains, Hel1 and Hel2, and an insert domain, Hel2i), and a C-terminal regulatory (CTR) domain. LGP2 lacks the two N-terminal CARDs but contains the DECH box domain, as well as the CTR domain. The CTR domain helps recognize non-self RNAs within the cellular environment. To facilitate the detection of a broad range of non-self RNA targets, each RLR contains a similar but divergent CTR domain that mediates RLR-specific interactions between bound nucleic acids or neighbouring patterns [PUBMED:24912143, PUBMED:25101084, PUBMED:22000018, PUBMED:18243112, PUBMED:19208642].