ArticleNature2014
Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 223 papers.
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Who cites it
223 citing papers in PubMed, 315 citations in OpenAlex.
- An ancient anthozoan protein reveals an alternative evolutionary path of antiviral signalling.Nature ecology & evolution · 2026Article
- Sensing of double-stranded RNA in human cells: molecular mechanisms and cellular consequences.Biochemical Society transactions · 2026Review
- Human RIG-I Antiviral Deficiency Caused by a Dominant-Negative Variant Locked in a Signaling-Inactive State.medRxiv : the preprint server for health sciences · 2026Article
- LncRNA-protein interactions: molecular switches for the precise regulation of innate immunity.Frontiers in immunology · 2026Review
- Old dogs-new tricks: multifaceted functions of MAVS beyond antivirus activity in human health and diseases.Cell & bioscience · 2025Review
- ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.Cell research · 2025Article
- Pattern recognition receptors and inflammasome: Now and beyond.Molecules and cells · 2025Review
- UNC0638 inhibits SARS-CoV-2 entry by blocking cathepsin L maturation.Journal of virology · 2025Article
- Anti-interferon armamentarium of human coronaviruses.Cellular and molecular life sciences : CMLS · 2025Review
- Influenza virus antagonizes self sensing by RIG-I to enhance viral replication.bioRxiv : the preprint server for biology · 2025Article
- A structural atlas of death domain fold proteins reveals their versatile roles in biology and function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comparative Genomics Provides Insights into Adaptive Evolution and Demographics of Bats.Molecular biology and evolution · 2024Article
- TRIM38 Induced in Respiratory Syncytial Virus-infected Cells Downregulates Type I Interferon Expression by Competing with TRIM25 to Bind RIG-I.Inflammation · 2024Article
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide.Journal of virology · 2024Article
- Article
- Identification of pigeon mitochondrial antiviral signaling protein (MAVS) and its role in antiviral innate immunity.Archives of virology · 2024Article
- Telomeres as hotspots for innate immunity and inflammation.DNA repair · 2024Review
- The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization.Nature communications · 2023Article
- SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.PLoS pathogens · 2023Article
163 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Ubiquitin (Ub) has important roles in a wide range of intracellular signalling pathways. In the conventional view, ubiquitin alters the signalling activity of the target protein through covalent modification, but accumulating evidence points to the emerging role of non-covalent interaction between ubiquitin and the target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I, both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63-Ubn) were shown to occur in its signalling domain, a tandem caspase activation and recruitment domain (hereafter referred to as 2CARD). Non-covalent binding of K63-Ubn to 2CARD induces its tetramer formation, a requirement for downstream signal activation. Here we report the crystal structure of the tetramer of human RIG-I 2CARD bound by three chains of K63-Ub2. 2CARD assembles into a helical tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a signalling platform for recruitment and activation of the downstream signalling molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD tetramer. The combination of structural and functional analyses reveals that binding avidity dictates the K63-linkage and chain-length specificity of 2CARD, and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD interaction and thus the 2CARD tetramer. Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.