2022
The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands
Wang W, Pyle AM. The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands. Molecular Cell 2022, 82: 4131-4144.e6. PMID: 36272408, PMCID: PMC9707737, DOI: 10.1016/j.molcel.2022.09.029.Peer-Reviewed Original ResearchConceptsRNA moleculesRNA ligandsHigh-resolution cryo-EM structuresCryo-EM structureDouble-stranded RNARIG-I receptorInduction of autoimmunityViral RNA moleculesAutoinhibited conformationInnate immune receptorsHost RNARelated RNAProtein foldsMolecular basisUnique molecular featuresHigh-affinity conformationAntiviral sensingHost cellsRNA virusesRNA releaseImmune receptorsRNAViral RNAExquisite selectivityMolecular features
2021
The molecular mechanism of RIG‐I activation and signaling
Thoresen D, Wang W, Galls D, Guo R, Xu L, Pyle AM. The molecular mechanism of RIG‐I activation and signaling. Immunological Reviews 2021, 304: 154-168. PMID: 34514601, PMCID: PMC9293153, DOI: 10.1111/imr.13022.Peer-Reviewed Original ResearchConceptsRIG-I activationTranscription of interferonEvolutionary implicationsAdapter proteinHost RNAPathogenic RNAsPattern recognition receptorsCell biologyInactive conformationMolecular mechanismsRNA virusesRole of RIGRNA duplexesInitial RNARNAStructural determinantsRecognition receptorsInnate immunityViral RNAInterferon expressionImportant receptorViral pathogensCellular spaceMolecular featuresReceptorsComprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms
Huston NC, Wan H, Strine MS, de Cesaris Araujo Tavares R, Wilen CB, Pyle AM. Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms. Molecular Cell 2021, 81: 584-598.e5. PMID: 33444546, PMCID: PMC7775661, DOI: 10.1016/j.molcel.2020.12.041.Peer-Reviewed Original ResearchConceptsRNA structureSecondary structureRNA virusesSARS-CoV-2 RNA genomeNovel regulatory motifsSingle-nucleotide resolutionDownstream functional analysisRNA drug targetsPositive-sense RNA virusesGenome architectureGenomic structureEvolutionary analysisRegulatory motifsSARS-CoV-2 genomeViral life cycleRNA genomeFunctional analysisGenomeDrug targetsPrimer designInfected cellsViral RNADepth structural analysisLife cycleΒ-coronavirus
2020
The Global and Local Distribution of RNA Structure throughout the SARS-CoV-2 Genome
de Cesaris Araujo Tavares R, Mahadeshwar G, Wan H, Huston NC, Pyle AM. The Global and Local Distribution of RNA Structure throughout the SARS-CoV-2 Genome. Journal Of Virology 2020, 95: 10.1128/jvi.02190-20. PMID: 33268519, PMCID: PMC8092842, DOI: 10.1128/jvi.02190-20.Peer-Reviewed Original ResearchSARS-CoV-2 genomeRNA structureRNA genomeRNA virusesViral genomeIndividual RNA structuresDrug targetsSARS-CoV-2 RNA genomeSilico pipelineMost RNA virusesRNA structural featuresComplex viral genomesRNA drug targetsStructured viral RNAsPotential drug targetsViral RNAViral infection cycleBase pair contentRNA biologyStructural ORFsLong genomeCellular mixturesGenomeRNA transcriptsInfection cycle
2014
The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain
Rawling DC, Kohlway AS, Luo D, Ding SC, Pyle AM. The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain. Nucleic Acids Research 2014, 42: 11601-11611. PMID: 25217590, PMCID: PMC4191399, DOI: 10.1093/nar/gku817.Peer-Reviewed Original ResearchConceptsATPase coreRetinoic acid-inducible gene IAcid-inducible gene INon-self RNASeries of mutationsActivity of RIGMetazoan cellsHelicase coreAllosteric controlTerminal domainPattern recognition receptorsAlpha-helixBiophysical analysisGene IAllosteric stabilizationType I interferonEnzymatic activityRecognition receptorsViral RNAStructural studiesRNAI interferonAdjacent domainsDomainImportant role