2024
Nanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy
Wang-Bishop L, Wehbe M, Pastora L, Yang J, Kimmel B, Garland K, Becker K, Carson C, Roth E, Gibson-Corley K, Ulkoski D, Krishnamurthy V, Fedorova O, Richmond A, Pyle A, Wilson J. Nanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy. ACS Nano 2024, 18: 11631-11643. PMID: 38652829, PMCID: PMC11080455, DOI: 10.1021/acsnano.3c06225.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDEAD Box Protein 58FemaleHumansImmunotherapyLipidsMiceMice, Inbred C57BLNanoparticlesTumor MicroenvironmentConceptsImmune checkpoint inhibitorsTumor microenvironmentLipid nanoparticlesBreast cancerResponse to ICIResponse to immune checkpoint inhibitorsInfiltration of CD8<sup>+</sup>Models of triple-negative breast cancerCD4<sup>+</sup> T cellsInhibition of tumor growthTriple-negative breast cancerRIG-IIonizable lipid nanoparticlesLung metastatic burdenIncrease tumor immunogenicityBreast tumor microenvironmentSignaling in vitroACTLA-4Immunogenic melanomaCheckpoint inhibitorsTumor immunogenicityImmunotherapeutic modalitiesCancer immunotherapyMetastatic burdenAPD-1
2023
The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization
Wang W, Götte B, Guo R, Pyle A. The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization. Nature Communications 2023, 14: 7308. PMID: 37951994, PMCID: PMC10640585, DOI: 10.1038/s41467-023-42982-0.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsCarrier ProteinsDEAD Box Protein 58DEAD-box RNA HelicasesImmunity, InnateLigandsRNA, Double-StrandedRNA, ViralConceptsRNA 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
Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3)
Li K, Zheng J, Wirawan M, Trinh NM, Fedorova O, Griffin PR, Pyle AM, Luo D. Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3). Nucleic Acids Research 2021, 49: 9978-9991. PMID: 34403472, PMCID: PMC8464030, DOI: 10.1093/nar/gkab712.Peer-Reviewed Original ResearchConceptsC-terminal domainN-terminal domainDRH-3RNA interferenceTandem caspase activationSimilar domain architectureEndogenous RNAi pathwaysRNA helicase familyDouble-stranded RNACARDs of RIGUnique structural dynamicsGermline developmentEvolutionary divergenceChromosome segregationRNAi pathwayCaenorhabditis elegansDomain architectureHelicase familyCaspase activationDistinct foldsRecruitment domainMolecular understandingRLR familyRNA duplexesRNA
2020
Small-Molecule Antagonists of the RIG‑I Innate Immune Receptor
Rawling DC, Jagdmann GE, Potapova O, Pyle AM. Small-Molecule Antagonists of the RIG‑I Innate Immune Receptor. ACS Chemical Biology 2020, 15: 311-317. PMID: 31944652, DOI: 10.1021/acschembio.9b00810.Peer-Reviewed Original ResearchConceptsInnate immune systemRIG-I receptorRole of RIGSmall molecule antagonistsPotent RIGAutoimmune disordersAntimicrobial therapyRange of diseasesImmune systemInterferon responseVertebrate innate immune systemImmune receptorsReceptorsNew drug design strategiesAntagonistRNA virusesDrug design strategiesCOPD
2019
RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling
Ren X, Linehan MM, Iwasaki A, Pyle AM. RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling. Cell Reports 2019, 29: 3807-3815.e3. PMID: 31851914, DOI: 10.1016/j.celrep.2019.11.052.Peer-Reviewed Original ResearchConceptsRNA moleculesRIG-I activationBase pair sequenceHost RNA moleculesViral RNA moleculesRIG-I recognitionMolecular basisRNA variantsRNA targetsPair sequenceHuman cellsBase pairsImmune receptorsMechanisms of evasionTerminal base pairsLigand affinityWhole animalInterferon responseDeadly pathogenRNA therapeuticsMarburg virusCellsOverhangMoleculesSignalingRNA binding activates RIG-I by releasing an autorepressed signaling domain
Dickey TH, Song B, Pyle AM. RNA binding activates RIG-I by releasing an autorepressed signaling domain. Science Advances 2019, 5: eaax3641. PMID: 31616790, PMCID: PMC6774723, DOI: 10.1126/sciadv.aax3641.Peer-Reviewed Original Research
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