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Title | The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 7308, Year 2023 |
Publish date | Nov 11, 2023 |
Authors | Wenshuai Wang / Benjamin Götte / Rong Guo / Anna Marie Pyle / |
PubMed Abstract | 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 ...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 links | Nat Commun / PubMed:37951994 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.2 - 4.0 Å |
Structure data | EMDB-29823: Cryo-EM structure of RNP end EMDB-29824: Cryo-EM structure of RNP end 2 EMDB-29825: Cryo-EM structure of RNP inter |
Chemicals | ChemComp-ZN: |
Source |
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Keywords | Transferase/Hydrolase/RNA / ribonucleoprotein complex / RNA sensor / RIG-I like receptor / Ubiquitination / E3 ligase / TRIM family / ANTIVIRAL PROTEIN / Transferase-Hydrolase-RNA complex |