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Title | Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA. |
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Journal, issue, pages | Elife, Vol. 13, Year 2024 |
Publish date | May 15, 2024 |
Authors | Claudia D Consalvo / Adedeji M Aderounmu / Helen M Donelick / P Joseph Aruscavage / Debra M Eckert / Peter S Shen / Brenda L Bass / |
PubMed Abstract | Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon ...Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense, Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1's helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways. |
External links | Elife / PubMed:38747717 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 Å |
Structure data | EMDB-41060, PDB-8t5s: |
Chemicals | ChemComp-ZN: ChemComp-MG: ChemComp-ADP: |
Source |
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Keywords | ANTIVIRAL PROTEIN/RNA / helicase / RLR / RIG-I-like Receptor / ATPase / dsRNA / ANTIVIRAL PROTEIN-RNA complex |