ArticleNucleic acids research2020
Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 82 citations in OpenAlex.
- Role of Pattern Recognition Receptors (PRRs) in Spinal Cord Injury (SCI): A Comprehensive Review.Molecular neurobiology · 2026Review
- Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5.European journal of medicinal chemistry · 2026Article
- MDA5 generates compact ribonucleoprotein complexes via ATP-dependent double-stranded RNA unwinding.Nucleic acids research · 2026Article
- Review
- Synthetic double-stranded RNA in antiviral immunity and vaccine adjuvant: insights into poly(I:C) and poly(A:U).Frontiers in immunology · 2026Review
- ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.Cell research · 2025Article
- The RIG-I-like receptor family of immune proteins.Molecular cell · 2025Review
- Immuno-metabolic diseases and therapeutics: molecular mechanisms via inflammasome signaling.Cell communication and signaling : CCS · 2025Review
- Pattern recognition receptors and inflammasome: Now and beyond.Molecules and cells · 2025Review
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- Identifying RNA Sensors in Antiviral Innate Immunity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Pyroptosis-immune cell cross talk in asthma: From molecular mechanisms to precision therapeutics.Frontiers in immunology · 2025Review
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- DDX RNA helicases: key players in cellular homeostasis and innate antiviral immunity.Journal of virology · 2024Review
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape.Pathogens (Basel, Switzerland) · 2024Review
- HOIL1 mediates MDA5 activation through ubiquitination of LGP2.bioRxiv : the preprint server for biology · 2024Article
- Crosstalk between vault RNAs and innate immunity.Molecular biology reports · 2024Review
- Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2.Nucleic acids research · 2024Article
- The competitive landscape of the dsRNA world.Molecular cell · 2024Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytoplasmic RIG-I-like receptor (RLR) proteins in mammalian cells recognize viral RNA and initiate an antiviral response that results in IFN-β induction. Melanoma differentiation-associated protein 5 (MDA5) forms fibers along viral dsRNA and propagates an antiviral response via a signaling domain, the tandem CARD. The most enigmatic RLR, laboratory of genetics and physiology (LGP2), lacks the signaling domain but functions in viral sensing through cooperation with MDA5. However, it remains unclear how LGP2 coordinates fiber formation and subsequent MDA5 activation. We utilized biochemical and biophysical approaches to observe fiber formation and the conformation of MDA5. LGP2 facilitated MDA5 fiber assembly. LGP2 was incorporated into the fibers with an average inter-molecular distance of 32 nm, suggesting the formation of hetero-oligomers with MDA5. Furthermore, limited protease digestion revealed that LGP2 induces significant conformational changes on MDA5, promoting exposure of its CARDs. Although the fibers were efficiently dissociated by ATP hydrolysis, MDA5 maintained its active conformation to participate in downstream signaling. Our study demonstrated the coordinated actions of LGP2 and MDA5, where LGP2 acts as an MDA5 nucleator and requisite partner in the conversion of MDA5 to an active conformation. We revealed a mechanistic basis for LGP2-mediated regulation of MDA5 antiviral innate immune responses.
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Registered trials
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.