ArticleNucleic acids research2015
High-resolution HDX-MS reveals distinct mechanisms of RNA recognition and activation by RIG-I and MDA5.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Mapping of RNA Helicase Dynamics by HDX-MS.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Glycosylation as a dynamic regulator of RLR and cGAS-STING innate immune signalling pathways.Communications biology · 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
- Review
- Review
- ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.Cell research · 2025Article
- Exploring the CNOT1(800-999) HEAT Domain and Its Interactions with Tristetraprolin (TTP) as Revealed by Hydrogen/Deuterium Exchange Mass Spectrometry.Biomolecules · 2025Article
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- Characterization of RNA driven structural changes in full length RIG-I leading to its agonism or antagonism.Nucleic acids research · 2023Article
- A loosened gating mechanism of RIG-I leads to autoimmune disorders.Nucleic acids research · 2022Article
- The intrinsically disordered CARDs-Helicase linker in RIG-I is a molecular gate for RNA proofreading.The EMBO journal · 2022Article
- The molecular mechanism of RIG-I activation and signaling.Immunological reviews · 2021Review
- Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3).Nucleic acids research · 2021Article
- Exploiting Knowledge on Structure-Activity Relationships for Designing Peptidomimetics of Endogenous Peptides.Biomedicines · 2021Review
- Auxiliary domains of the HrpB bacterial DExH-box helicase shape its RNA preferences.RNA biology · 2020Article
- Integrative structural biology studies of HIV-1 reverse transcriptase binding to a high-affinity DNA aptamer.Current research in structural biology · 2020Article
- RNA binding activates RIG-I by releasing an autorepressed signaling domain.Science advances · 2019Article
- MS-Based Approaches Enable the Structural Characterization of Transcription Factor/DNA Response Element Complex.Biomolecules · 2019Article
- Therapeutic Targeting of RIG-I and MDA5 Might Not Lead to the Same Rome.Trends in pharmacological sciences · 2019Review
- Applications of In-Cell NMR in Structural Biology and Drug Discovery.International journal of molecular sciences · 2019Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RIG-I and MDA5 are the major intracellular immune receptors that recognize viral RNA species and undergo a series of conformational transitions leading to the activation of the interferon-mediated antiviral response. However, to date, full-length RLRs have resisted crystallographic efforts and a molecular description of their activation pathways remains hypothetical. Here we employ hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) to probe the apo states of RIG-I and MDA5 and to dissect the molecular details with respect to distinct RNA species recognition, ATP binding and hydrolysis and CARDs activation. We show that human RIG-I maintains an auto-inhibited resting state owing to the intra-molecular HEL2i-CARD2 interactions while apo MDA5 lacks the analogous intra-molecular interactions and therefore adopts an extended conformation. Our work demonstrates that RIG-I binds and responds differently to short triphosphorylated RNA and long duplex RNA and that sequential addition of RNA and ATP triggers specific allosteric effects leading to RIG-I CARDs activation. We also present a high-resolution protein surface mapping technique that refines the cooperative oligomerization model of neighboring MDA5 molecules on long duplex RNA. Taken together, our data provide a high-resolution view of RLR activation in solution and offer new evidence for the molecular mechanism of RLR activation.
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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.