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TitleThe E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 7308, Year 2023
Publish dateNov 11, 2023
AuthorsWenshuai Wang / Benjamin Götte / Rong Guo / Anna Marie Pyle /
PubMed AbstractRIG-I is an essential innate immune receptor that responds to infection by RNA viruses. The RIG-I signaling cascade is mediated by a series of post-translational modifications, the most important of ...RIG-I is an essential innate immune receptor that responds to infection by RNA viruses. The RIG-I signaling cascade is mediated by a series of post-translational modifications, the most important of which is ubiquitination of the RIG-I Caspase Recruitment Domains (CARDs) by E3 ligase Riplet. This is required for interaction between RIG-I and its downstream adapter protein MAVS, but the mechanism of action remains unclear. Here we show that Riplet is required for RIG-I signaling in the presence of both short and long dsRNAs, establishing that Riplet activation does not depend upon RIG-I filament formation on long dsRNAs. Likewise, quantitative Riplet-RIG-I affinity measurements establish that Riplet interacts with RIG-I regardless of whether the receptor is bound to RNA. To understand this, we solved high-resolution cryo-EM structures of RIG-I/RNA/Riplet complexes, revealing molecular interfaces that control Riplet-mediated activation and enabling the formulation of a unified model for the role of Riplet in signaling.
External linksNat Commun / PubMed:37951994 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.0 Å
Structure data

EMDB-29823: Cryo-EM structure of RNP end
PDB-8g7t: Cryo-EM structure of Riplet:RIG-I:dsRNA complex (end-end)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-29824: Cryo-EM structure of RNP end 2
PDB-8g7u: Cryo-EM structure of Riplet:RIG-I:dsRNA complex (end-semi-closed end)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-29825: Cryo-EM structure of RNP inter
PDB-8g7v: Cryo-EM structure of Riplet:RIG-I:dsRNA complex (end-inter)
Method: EM (single particle) / Resolution: 3.9 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsTransferase/Hydrolase/RNA / ribonucleoprotein complex / RNA sensor / RIG-I like receptor / Ubiquitination / E3 ligase / TRIM family / ANTIVIRAL PROTEIN / Transferase-Hydrolase-RNA complex

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