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Structure paper

Title Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA.
Journal, issue, pagesElife, Vol. 13, Year 2024
Publish dateMay 15, 2024
AuthorsClaudia D Consalvo / Adedeji M Aderounmu / Helen M Donelick / P Joseph Aruscavage / Debra M Eckert / Peter S Shen / Brenda L Bass /
PubMed AbstractInvertebrates 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 linksElife / PubMed:38747717 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 7.6 Å
Structure data

41060

8t5s

EMDB-41060, PDB-8t5s:
Cryo-EM structure of DRH-1 helicase and C-terminal domain bound to dsRNA
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-43430: Cryo-EM structure of C. elegans antiviral complex Dicer-1, DRH-1, and RDE-4 bound to one dsRNA
Method: EM (single particle) / Resolution: 6.1 Å

EMDB-43431: Cryo-EM structure of C. elegans antiviral complex Dicer-1, DRH-1, and RDE-4 bound to two dsRNA
Method: EM (single particle) / Resolution: 7.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-MG:
Unknown entry

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • caenorhabditis elegans (invertebrata)
  • synthetic construct (others)
KeywordsANTIVIRAL PROTEIN/RNA / helicase / RLR / RIG-I-like Receptor / ATPase / dsRNA / ANTIVIRAL PROTEIN-RNA complex

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