FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2026573757> ?p ?o ?g. }

• W2026573757 endingPage "507" @default.
• W2026573757 startingPage "505" @default.
• W2026573757 abstract "A new study (Wu et al., 2014Wu B. Peisley A. Tetrault D. Li Z. Egelman E.H. Magor K.E. Walz T. Penczek P.A. Hur S. Mol. Cell. 2014; 55 (this issue): 511-523Google Scholar) employs X-ray crystallography and cryoelectron microscopy (cryo-EM) to reveal how the caspase activation and recruitment domains (CARDs) of the cytosolic viral RNA sensor RIG-I nucleate the formation of large CARD filaments of the mitochondrial antiviral signaling protein MAVS to trigger the antiviral innate immune response. A new study (Wu et al., 2014Wu B. Peisley A. Tetrault D. Li Z. Egelman E.H. Magor K.E. Walz T. Penczek P.A. Hur S. Mol. Cell. 2014; 55 (this issue): 511-523Google Scholar) employs X-ray crystallography and cryoelectron microscopy (cryo-EM) to reveal how the caspase activation and recruitment domains (CARDs) of the cytosolic viral RNA sensor RIG-I nucleate the formation of large CARD filaments of the mitochondrial antiviral signaling protein MAVS to trigger the antiviral innate immune response. Intruding microbes are rapidly detected by the innate immune system, which provides an immediate defense to infection and activates the adaptive immune response. The innate immune system distinguishes self from nonself by detecting generic pathogen-associated molecular patterns (PAMPs) such as cytosolic viral RNA, endosomal nucleic acids, or bacterial cell wall and membrane components. PAMPs are detected by germline-encoded pattern recognition receptors (PPRs), e.g., RIG-I like receptors, which sense cytosolic viral RNA, or Toll like receptors, which sense different types of PAMPs in endosomes or on the cell surface. PRRs are activated through their interaction with the specific ligands, typically via conformational changes and/or oligomer formation. The PRR-PAMP complexes trigger signaling cascades that initiate the production of type I interferons and proinflammatory cytokines, resulting in the expression of hundreds of response genes. Critical components of many of these signaling pathways are the adaptor or mediator proteins, which link the activation of PRRs by PAMPs to the activation of downstream factors, such as kinases, ubiquitin-ligases, or caspases. MAVS (mitochondrial antiviral signaling protein, also known as VISA, IPS1, and Cardif) is an adaptor protein that contains a caspase activation and recruitment domain (CARD), a linker region with interaction sites for downstream factors, and a transmembrane domain that anchors MAVS to the surface of mitochondria and peroxisomes. In this issue, Wu et al. have now resolved the way RIG-I activates MAVS at atomic resolution (Wu et al., 2014Wu B. Peisley A. Tetrault D. Li Z. Egelman E.H. Magor K.E. Walz T. Penczek P.A. Hur S. Mol. Cell. 2014; 55 (this issue): 511-523Google Scholar). MAVS is activated by the cytosolic viral RNA sensors RIG-I (retinoic acid inducible I) and the related MDA5 (melanoma differentiation antigen 5) (Figure 1). RIG-I and MDA5 preferentially respond to 5′ triphosphate-containing double-stranded RNA (ppp-dsRNA) or to long dsRNA, respectively. ppp-dsRNA triggers a conformational change in RIG-I that leads to the exposure of its tandem CARDs, which in the absence of RNA ligands are masked by interaction with the RNA binding superfamily 2 ATPase module (Kowalinski et al., 2011Kowalinski E. Lunardi T. McCarthy A.A. Louber J. Brunel J. Grigorov B. Gerlier D. Cusack S. Cell. 2011; 147: 423-435Abstract Full Text Full Text PDF PubMed Scopus (411) Google Scholar). A central finding for understanding the role of MAVS in antiviral innate immunity was the observation that it polymerizes into large filament structures (Hou et al., 2011Hou F. Sun L. Zheng H. Skaug B. Jiang Q.X. Chen Z.J. Cell. 2011; 146: 448-461Abstract Full Text Full Text PDF PubMed Scopus (745) Google Scholar). These filaments are proteinaceous platforms to recruit and colocalize downstream factors such as the E3 ubiquitin ligases TNF-α receptor-associated factors (TRAFs). While polymer formation of MAVS provides a satisfying explanation for its role as signaling adaptor, how RIG-I initiates this process remained elusive. Recent work showed that RIG-I itself has the capability to form defined CARD oligomers upon interaction with RNA ligands: four copies of the N-terminal tandem CARDs of RIG-I form a helical assembly that is stabilized by binding of K62-linked ubiquitin chains across its subunits (Peisley et al., 2014Peisley A. Wu B. Xu H. Chen Z.J. Hur S. Nature. 2014; 509: 110-114Crossref PubMed Scopus (207) Google Scholar). TRIM25-dependent formation of K63 ubiquitin chains is essential for RIG-I-mediated MAVS activation (Gack et al., 2007Gack M.U. Shin Y.C. Joo C.H. Urano T. Liang C. Sun L. Takeuchi O. Akira S. Chen Z. Inoue S. Jung J.U. Nature. 2007; 446: 916-920Crossref PubMed Scopus (1051) Google Scholar). Importantly, the CARDs in the RIG-I oligomer were found to have a helical arrangement, somewhat similar to the helical arrangement of the death domain (DDs) oligomers in the MyD88-IRAK2-IRAK4 signaling mediator complex (Lin et al., 2010Lin S.C. Lo Y.C. Wu H. Nature. 2010; 465: 885-890Crossref PubMed Scopus (676) Google Scholar). The helical structure of the RIG-I CARD oligomers raised the possibility that other CARD domain oligomers—in particular MAVS—might adopt a similar helical architecture. Hur and coworkers addressed this question and determined the cryo-EM structure of the MAVS CARD filament to 3.6 Å resolution. The near-atomic resolution of the helical filament—a result of recent advances in electron detector technologies and image processing algorithms (Lu et al., 2014Lu A. Magupalli V.G. Ruan J. Yin Q. Atianand M.K. Vos M.R. Schröder G.F. Fitzgerald K.A. Wu H. Egelman E.H. Cell. 2014; 156: 1193-1206Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar)—enabled the generation of a refined atomic model. Indeed, the mutual interfaces of the different CARDs in the MAVS filament was found to be the same as between the CARDs of RIG-I oligomers (Peisley et al., 2014Peisley A. Wu B. Xu H. Chen Z.J. Hur S. Nature. 2014; 509: 110-114Crossref PubMed Scopus (207) Google Scholar). The observation that RIG-I CARDs and MAVS CARDs assemble in similar ways immediately posed the question as to how these two oligomers interact and whether RIG-I triggers MAVS polymerization by forming a nucleation site. Such a model could be elegantly answered by the structure of a complex or RIG-I CARDs and MAVS CARDs. However, the unrestricted oligomerization of MAVS CARDs is a technical obstacle for the generation of a defined complex for crystallization. Hur and coworkers solved this problem in an elegant way, by generating a sterically restricted fusion protein between the RIG-I tandem CARDs and the MAVS CARD. This defined complex could be crystallized and resulted in a 3.4 Å crystal structure that shows that the MAVS CARDs bound to the RIG-I tandem CARD tetramer resemble the helical arrangement of the CARDs in the MAVS filament. Thus, the RNA- and ubiquitin-dependent formation of a RIG-I CARD oligomer nucleates MAVS filament formation, similar to the role of nucleation in the crystallization of a supersaturated solution of proteins. The resulting MAVS filaments are linked to mitochondria via the transmembrane and linker domains (Figure 1). Of note, an independently reported cryo-EM reconstruction of MAVS CARD filaments at 9.6 Å resolution came to a somewhat different conclusion (Xu et al., 2014Xu H. He X. Zheng H. Huang L.J. Hou F. Yu Z. de la Cruz M.J. Borkowski B. Zhang X. Chen Z.J. Jiang Q.X. Elife (Cambridge). 2014; 3: e01489Google Scholar). The filament reconstruction in that report showed a different geometry, and the authors concluded that MAVS filaments have a distinct CARD interaction geometry. While the nature of the differences between the two filament models needs to be resolved in future studies, Xu et al. also analyzed MAVS filaments by superresolution light microscopy in living cells. They observe, remarkably, that most if not all MAVS of a cell is eventually incorporated into filaments of about 400 nm length, and filaments may even contain MAVS from different mitochondria. Thus, MAVS polymerization appears to be an “all or none” switch, massively amplifying the signal. How are these filaments dissolved and where does the energy come from? Many filament-forming proteins such as actin, tubulin, the DNA repair protein Rad51, and the RNA sensor MDA5 are nucleoside triphosphatases. ATP/GTP turnover enables an intrinsically dynamic nature of those filaments, often controlled by regulating factors. However, MAVS filaments appear to be very stable and have prion-like properties (Cai et al., 2014Cai X. Chen J. Xu H. Liu S. Jiang Q.X. Halfmann R. Chen Z.J. Cell. 2014; 156: 1207-1222Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar); thus the nature of the dissolution of MAVS filaments is a central question for future studies. Perhaps autophagy and the NLRX1 NOD-like ATPase, which are known to negatively regulate RIG-I signaling, play a critical role here (for review, see Galluzzi et al., 2012Galluzzi L. Kepp O. Kroemer G. Nat. Rev. Mol. Cell Biol. 2012; 13: 780-788Crossref PubMed Scopus (443) Google Scholar). Finally, recent structural studies showed a similar nucleation and polymerization mechanism in inflammatory responses: the PYRIN domain of ASC forms long filaments that are nucleated by oligomers of AIM2 or NLRP3 “inflammasomes” (Cai et al., 2014Cai X. Chen J. Xu H. Liu S. Jiang Q.X. Halfmann R. Chen Z.J. Cell. 2014; 156: 1207-1222Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar, Lu et al., 2014Lu A. Magupalli V.G. Ruan J. Yin Q. Atianand M.K. Vos M.R. Schröder G.F. Fitzgerald K.A. Wu H. Egelman E.H. Cell. 2014; 156: 1193-1206Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar). PYRIN domains, CARDs, and DDs constitute a structurally related superfamily of signal adaptor proteins. Importantly, the PYRIN domains of ASC assemble into a helical filament (Lu et al., 2014Lu A. Magupalli V.G. Ruan J. Yin Q. Atianand M.K. Vos M.R. Schröder G.F. Fitzgerald K.A. Wu H. Egelman E.H. Cell. 2014; 156: 1193-1206Abstract Full Text Full Text PDF PubMed Scopus (625) Google Scholar) that is topologically similar to the MAVS CARD filament and to the helical arrangement of DDs in the MyD88-IRAK2-IRAK4 “Myddosome” (Lin et al., 2010Lin S.C. Lo Y.C. Wu H. Nature. 2010; 465: 885-890Crossref PubMed Scopus (676) Google Scholar). Thus, nucleated triggering of oligomerization or polymerization of DD superfamily proteins emerges as a central feature of innate immune signaling. Once we have a better understanding of not only nucleation but also the removal of the filaments, the molecular logic for the evolution of protein polymerization or enzymatic cascades in different signaling pathways should become clear. Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-IWu et al.Molecular CellJuly 10, 2014In BriefA viral RNA sensor, RIG-I, activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Wu et al. show that RIG-I acts as a template for the CARDMAVS filament assembly by forming a helical tetrameric structure and recruiting individual CARDMAVS along its extended helical trajectory. Full-Text PDF Open Archive" @default.
• W2026573757 created "2016-06-24" @default.
• W2026573757 creator A5063163809 @default.
• W2026573757 date "2014-08-01" @default.
• W2026573757 modified "2023-09-28" @default.
• W2026573757 title "RIG-I Holds the CARDs in a Game of Self versus Nonself" @default.
• W2026573757 cites W1973610263 @default.
• W2026573757 cites W1993211211 @default.
• W2026573757 cites W1994034344 @default.
• W2026573757 cites W2053476949 @default.
• W2026573757 cites W2067706259 @default.
• W2026573757 cites W2078819049 @default.
• W2026573757 cites W2078850432 @default.
• W2026573757 cites W2160434954 @default.
• W2026573757 cites W2167049000 @default.
• W2026573757 cites W2169890153 @default.
• W2026573757 doi "https://doi.org/10.1016/j.molcel.2014.08.009" @default.
• W2026573757 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25148359" @default.
• W2026573757 hasPublicationYear "2014" @default.
• W2026573757 type Work @default.
• W2026573757 sameAs 2026573757 @default.
• W2026573757 citedByCount "6" @default.
• W2026573757 countsByYear W20265737572016 @default.
• W2026573757 countsByYear W20265737572017 @default.
• W2026573757 countsByYear W20265737572020 @default.
• W2026573757 countsByYear W20265737572022 @default.
• W2026573757 crossrefType "journal-article" @default.
• W2026573757 hasAuthorship W2026573757A5063163809 @default.
• W2026573757 hasBestOaLocation W20265737571 @default.
• W2026573757 hasConcept C70721500 @default.
• W2026573757 hasConcept C86803240 @default.
• W2026573757 hasConceptScore W2026573757C70721500 @default.
• W2026573757 hasConceptScore W2026573757C86803240 @default.
• W2026573757 hasIssue "4" @default.
• W2026573757 hasLocation W20265737571 @default.
• W2026573757 hasLocation W20265737572 @default.
• W2026573757 hasOpenAccess W2026573757 @default.
• W2026573757 hasPrimaryLocation W20265737571 @default.
• W2026573757 hasRelatedWork W1641042124 @default.
• W2026573757 hasRelatedWork W1990804418 @default.
• W2026573757 hasRelatedWork W1993764875 @default.
• W2026573757 hasRelatedWork W2013243191 @default.
• W2026573757 hasRelatedWork W2046158694 @default.
• W2026573757 hasRelatedWork W2082860237 @default.
• W2026573757 hasRelatedWork W2117258802 @default.
• W2026573757 hasRelatedWork W2130076355 @default.
• W2026573757 hasRelatedWork W2151865869 @default.
• W2026573757 hasRelatedWork W4234157524 @default.
• W2026573757 hasVolume "55" @default.
• W2026573757 isParatext "false" @default.
• W2026573757 isRetracted "false" @default.
• W2026573757 magId "2026573757" @default.
• W2026573757 workType "article" @default.