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C-terminal domain of Retinoic acid-inducible gene (RIG)-I-like Receptors, Cereblon (CRBN), and similar protein domains Retinoic acid-inducible gene (RIG)-I-like Receptors (RLRs) are cytoplasmic RNA receptors that recognize non-self RNA and act as molecular sensors to detect viral pathogens. They play crucial roles in innate antiviral responses, including the production of proinflammatory cytokines and type I interferon. There are three RLRs in vertebrates, RIG-I, LGP2, and MDA5. They are characterized by a central DExD/H-box helicase domain and a C-terminal domain, both of which are responsible for binding viral RNA. Cereblon is part of an E3 ubiquitin ligase complex, together with damaged DNA binding protein 1 (DDB1), CUL4A and ROC1. Cereblon interacts directly with DDB1, although the C-terminal domain characterized here does not contribute to that interaction. The C-terminal domain of Cereblon was shown to contain the binding site for thalidomide and its analogs, a class of teratogenic drugs that exhibit an antiproliferative effect on myelomas. Mutations in CRBN, some of which map onto the C-terminal domain, were associated with autosomal recessive mental retardation, which may have to do with interactions between CRBN and ion channels in the brain. RLRs and Cereblon contain a common conserved zinc binding site in their C-terminal domains. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",