Skip to main content
SpringerLink
Log in

Structures of RIG-I-Like Receptors and Insights into Viral RNA Sensing

  • Chapter
  • First Online:
Structural Immunology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1172))

Abstract

RIG-I-like receptors (RLRs) are an important family of pattern recognition receptors. They activate the immunological responses against viral infections by sensing RNAs in the cytoplasm. Recent studies provide significant insights into the activation and transduction mechanisms of RLRs family (members including RIG-I, MDA5, and LGP2). Here we review our current understanding of the structures of RLRs. Structural characterizations of RLRs family have revealed the mechanism of their actions at molecular level. The activation mechanisms of RIG-I and MDA5 are different, despite both of them have similar domain organizations and bind to dsRNA ligands. RIG-I, but not MDA5, adopts an auto-suppression conformation in the absence of RNA. In addition to ligand triggered receptor oligomerization, the activities of these receptors are also regulated by several posttranslational modifications, especially ubiquitination. Overall, these structural studies play critical roles in promoting the understanding of viral RNA recognition mechanisms by the host innate immune system, which also contribute to the designing of drugs for treatment of viral infection. However, much work remains to be done in studying the signaling pathway of MDA5 and LGP2, particularly by structural biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124(4):783–801

    Article  CAS  PubMed  Google Scholar 

  2. Meylan E, Tschopp J, Karin M (2006) Intracellular pattern recognition receptors in the host response. Nature 442(7098):39–44

    Article  CAS  PubMed  Google Scholar 

  3. D’Cruz AA et al (2018) Identification of a second binding site on the TRIM25 B30.2 domain. Biochem J 475(2):429–440

    Article  CAS  Google Scholar 

  4. Thompson AJ, Locarnini SA (2007) Toll-like receptors, RIG-I-like RNA helicases and the antiviral innate immune response. Immunol Cell Biol 85(6):435–445

    Article  CAS  PubMed  Google Scholar 

  5. Pichlmair A, Reis e Sousa C (2007) Innate recognition of viruses. Immunity 27(3):370–383

    Article  CAS  PubMed  Google Scholar 

  6. Yoneyama M, Fujita T (2007) Function of RIG-I-like receptors in antiviral innate immunity. J Biol Chem 282(21):15315–15318

    Article  CAS  PubMed  Google Scholar 

  7. Berke IC, Li Y, Modis Y (2013) Structural basis of innate immune recognition of viral RNA. Cell Microbiol 15(3):386–394

    Article  CAS  PubMed  Google Scholar 

  8. Yoneyama M et al (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5(7):730–737

    Article  CAS  PubMed  Google Scholar 

  9. Yoneyama M et al (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175(5):2851–2858

    Article  CAS  PubMed  Google Scholar 

  10. Kawai T, Akira S (2006) Innate immune recognition of viral infection. Nat Immunol 7(2):131–137

    Article  CAS  PubMed  Google Scholar 

  11. Seth RB, Sun L, Chen ZJ (2006) Antiviral innate immunity pathways. Cell Res 16(2):141–147

    Article  CAS  PubMed  Google Scholar 

  12. Kato H et al (2005) Cell type-specific involvement of RIG-I in antiviral response. Immunity 23(1):19–28

    Article  CAS  PubMed  Google Scholar 

  13. Gitlin L et al (2006) Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA 103(22):8459–8464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kato H et al (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441(7089):101–105

    Article  CAS  PubMed  Google Scholar 

  15. Kawai T et al (2005) IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6(10):981–988

    Article  CAS  PubMed  Google Scholar 

  16. Sumpter R Jr et al (2005) Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J Virol 79(5):2689–2699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li K et al (2005) Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. J Biol Chem 280(17):16739–16747

    Article  CAS  PubMed  Google Scholar 

  18. Hornung V et al (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314(5801):994–997

    Article  PubMed  Google Scholar 

  19. McCartney SA et al (2008) MDA-5 recognition of a murine norovirus. PLoS Pathog 4(7):e1000108

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Loo YM et al (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82(1):335–345

    Article  CAS  PubMed  Google Scholar 

  21. Park HH et al (2007) Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex. Cell 128(3):533–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin SC, Lo YC, Wu H (2010) Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 465(7300):885–890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Qi S et al (2010) Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell 141(3):446–457

    Article  CAS  PubMed  Google Scholar 

  24. Hou F et al (2011) MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 146(3):448–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yuan S et al (2011) Structure of the Drosophila apoptosome at 6.9 a resolution. Structure 19(1):128–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Meylan E et al (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437(7062):1167–1172

    Article  CAS  PubMed  Google Scholar 

  27. Seth RB et al (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122(5):669–682

    Article  CAS  PubMed  Google Scholar 

  28. Xu LG et al (2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19(6):727–740

    Article  CAS  PubMed  Google Scholar 

  29. Gorbalenya AE et al (1988) A novel superfamily of nucleoside triphosphate-binding motif containing proteins which are probably involved in duplex unwinding in DNA and RNA replication and recombination. FEBS Lett 235(1–2):16–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hopfner KP, Michaelis J (2007) Mechanisms of nucleic acid translocases: lessons from structural biology and single-molecule biophysics. Curr Opin Struct Biol 17(1):87–95

    Article  CAS  PubMed  Google Scholar 

  31. Fujita T et al (2007) Triggering antiviral response by RIG-I-related RNA helicases. Biochimie 89(6–7):754–760

    Article  CAS  PubMed  Google Scholar 

  32. Wang Y et al (2010) Structural and functional insights into 5′-ppp RNA pattern recognition by the innate immune receptor RIG-I. Nat Struct Mol Biol 17(7):781–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Saito T et al (2007) Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA 104(2):582–587

    Article  CAS  PubMed  Google Scholar 

  34. Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6(9):644–658

    Article  CAS  PubMed  Google Scholar 

  35. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384

    Article  CAS  PubMed  Google Scholar 

  36. Ramos HJ, Gale M Jr (2011) RIG-I like receptors and their signaling crosstalk in the regulation of antiviral immunity. Curr Opin Virol 1(3):167–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Loo YM, Gale M Jr (2011) Immune signaling by RIG-I-like receptors. Immunity 34(5):680–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Leung DW, Amarasinghe GK (2012) Structural insights into RNA recognition and activation of RIG-I-like receptors. Curr Opin Struct Biol 22(3):297–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gack MU et al (2007) TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446(7138):916–920

    Article  CAS  PubMed  Google Scholar 

  40. Zeng W et al (2010) Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141(2):315–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pichlmair A et al (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314(5801):997–1001

    Article  CAS  PubMed  Google Scholar 

  42. Gee P et al (2008) Essential role of the N-terminal domain in the regulation of RIG-I ATPase activity. J Biol Chem 283(14):9488–9496

    Article  CAS  PubMed  Google Scholar 

  43. Myong S et al (2009) Cytosolic viral sensor RIG-I is a 5′-triphosphate-dependent translocase on double-stranded RNA. Science 323(5917):1070–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Matsumiya T, Stafforini DM (2010) Function and regulation of retinoic acid-inducible gene-I. Crit Rev Immunol 30(6):489–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chattopadhyay S et al (2010) Viral apoptosis is induced by IRF-3-mediated activation of Bax. EMBO J 29(10):1762–1773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kubler K et al (2010) Targeted activation of RNA helicase retinoic acid-inducible gene-I induces proimmunogenic apoptosis of human ovarian cancer cells. Cancer Res 70(13):5293–5304

    Article  PubMed  CAS  Google Scholar 

  47. Poeck H et al (2008) 5′-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med 14(11):1256–1263

    Article  CAS  PubMed  Google Scholar 

  48. Zitvogel L, Kroemer G (2009) Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects. J Clin Invest 119(8):2127–2130

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Gack MU et al (2010) Phosphorylation-mediated negative regulation of RIG-I antiviral activity. J Virol 84(7):3220–3229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mi Z et al (2010) SUMOylation of RIG-I positively regulates the type I interferon signaling. Protein Cell 1(3):275–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kowalinski E et al (2011) Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell 147(2):423–435

    Article  CAS  PubMed  Google Scholar 

  52. Peisley A et al (2014) Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature 509(7498):110–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gack MU et al (2008) Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction. Proc Natl Acad Sci USA 105(43):16743–16748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ferrage F et al (2012) Structure and dynamics of the second CARD of human RIG-I provide mechanistic insights into regulation of RIG-I activation. Structure 20(12):2048–2061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gao D et al (2009) REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PLoS ONE 4(6):e5760

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Maharaj NP et al (2012) Conventional protein kinase C-alpha (PKC-alpha) and PKC-beta negatively regulate RIG-I antiviral signal transduction. J Virol 86(3):1358–1371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Nistal-Villan E et al (2010) Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production. J Biol Chem 285(26):20252–20261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Luo D et al (2011) Structural insights into RNA recognition by RIG-I. Cell 147(2):409–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Civril F et al (2011) The RIG-I ATPase domain structure reveals insights into ATP-dependent antiviral signalling. EMBO Rep 12(11):1127–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Cui S et al (2008) The C-terminal regulatory domain is the RNA 5′-triphosphate sensor of RIG-I. Mol Cell 29(2):169–179

    Article  CAS  PubMed  Google Scholar 

  61. Takahasi K et al (2008) Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell 29(4):428–440

    Article  CAS  PubMed  Google Scholar 

  62. Lu C et al (2011) Crystal structure of RIG-I C-terminal domain bound to blunt-ended double-strand RNA without 5′ triphosphate. Nucleic Acids Res 39(4):1565–1575

    Article  CAS  PubMed  Google Scholar 

  63. Lu C et al (2010) The structural basis of 5′ triphosphate double-stranded RNA recognition by RIG-I C-terminal domain. Structure 18(8):1032–1043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jiang F et al (2011) Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature 479(7373):423–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Bamming D, Horvath CM (2009) Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2. J Biol Chem 284(15):9700–9712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kohlway A et al (2013) Defining the functional determinants for RNA surveillance by RIG-I. EMBO Rep 14(9):772–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Luo D et al (2012) Visualizing the determinants of viral RNA recognition by innate immune sensor RIG-I. Structure 20(11):1983–1988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ramanathan A et al (2016) The autoinhibitory CARD2-Hel2i Interface of RIG-I governs RNA selection. Nucleic Acids Res 44(2):896–909

    Article  CAS  PubMed  Google Scholar 

  69. Devarkar SC et al (2016) Structural basis for m7G recognition and 2′-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I. Proc Natl Acad Sci USA 113(3):596–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Fairman-Williams ME, Guenther UP, Jankowsky E (2010) SF1 and SF2 helicases: family matters. Curr Opin Struct Biol 20(3):313–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jiang X et al (2012) Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity 36(6):959–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Peisley A et al (2013) RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner. Mol Cell 51(5):573–583

    Article  CAS  PubMed  Google Scholar 

  73. Wu B et al (2014) Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I. Mol Cell 55(4):511–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wu H (2004) Assembly of post-receptor signaling complexes for the tumor necrosis factor receptor superfamily. Adv Protein Chem 68:225–279

    Article  CAS  PubMed  Google Scholar 

  75. Kageyama M et al (2011) 55 Amino acid linker between helicase and carboxyl terminal domains of RIG-I functions as a critical repression domain and determines inter-domain conformation. Biochem Biophys Res Commun 415(1):75–81

    Article  CAS  PubMed  Google Scholar 

  76. Deimling T et al (2014) Crystal and solution structure of the human RIG-I SF2 domain. Acta Crystallogr F Struct Biol Commun 70(Pt 8):1027–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Peisley A et al (2011) Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. Proc Natl Acad Sci USA 108(52):21010–21015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Baril M et al (2009) MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease. J Virol 83(3):1299–1311

    Article  CAS  PubMed  Google Scholar 

  79. Tang ED, Wang CY (2009) MAVS self-association mediates antiviral innate immune signaling. J Virol 83(8):3420–3428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kang DC et al (2002) mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci U S A 99(2):637–642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kovacsovics M et al (2002) Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation. Curr Biol 12(10):838–843

    Article  CAS  PubMed  Google Scholar 

  82. Andrejeva J et al (2004) The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci USA 101(49):17264–17269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Nejentsev S et al (2009) Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324(5925):387–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Aida K et al (2011) RIG-I- and MDA5-initiated innate immunity linked with adaptive immunity accelerates beta-cell death in fulminant type 1 diabetes. Diabetes 60(3):884–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Diao F et al (2007) Negative regulation of MDA5-but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase. Proc Natl Acad Sci USA 104(28):11706–11711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Fu J et al (2011) MDA5 is SUMOylated by PIAS2beta in the upregulation of type I interferon signaling. Mol Immunol 48(4):415–422

    Article  CAS  PubMed  Google Scholar 

  87. Takashima K, Oshiumi H, Seya T (2015) RIOK3 keeps MDA5 inactive. Oncotarget 6(31):30423–30424

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wu B et al (2013) Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell 152(1–2):276–289

    Article  CAS  PubMed  Google Scholar 

  89. Lang X et al (2017) TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity. J Exp Med 214(2):459–473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Berke IC, Modis Y (2012) MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA. EMBO J 31(7):1714–1726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Uchikawa E et al (2016) Structural analysis of dsRNA binding to anti-viral pattern recognition receptors LGP2 and MDA5. Mol Cell 62(4):586–602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Berke IC et al (2012) MDA5 assembles into a polar helical filament on dsRNA. Proc Natl Acad Sci USA 109(45):18437–18441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kato H et al (2008) Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205(7):1601–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ranjith-Kumar CT et al (2009) Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor. J Biol Chem 284(2):1155–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Binder M et al (2011) Molecular mechanism of signal perception and integration by the innate immune sensor retinoic acid-inducible gene-I (RIG-I). J Biol Chem 286(31):27278–27287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Pichlmair A et al (2009) Activation of MDA5 requires higher-order RNA structures generated during virus infection. J Virol 83(20):10761–10769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. del Toro Duany Y, Wu B, Hur S (2015) MDA5-filament, dynamics and disease. Curr Opin Virol 12:20–25

    Google Scholar 

  98. Arimoto K et al (2007) Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci USA 104(18):7500–7505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Komuro A, Bamming D, Horvath CM (2008) Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Cytokine 43(3):350–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Pippig DA et al (2009) The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA. Nucleic Acids Res 37(6):2014–2025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Rothenfusser S et al (2005) The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol 175(8):5260–5268

    Article  CAS  PubMed  Google Scholar 

  102. Rodriguez KR, Bruns AM, Horvath CM (2014) MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction. J Virol 88(15):8194–8200

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Zhu Z et al (2014) The laboratory of genetics and physiology 2: emerging insights into the controversial functions of this RIG-I-like receptor. Biomed Res Int 2014:960190

    PubMed  PubMed Central  Google Scholar 

  104. Komuro A, Horvath CM (2006) RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2. J Virol 80(24):12332–12342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Murali A et al (2008) Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response. J Biol Chem 283(23):15825–15833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Venkataraman T et al (2007) Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol 178(10):6444–6455

    Article  CAS  PubMed  Google Scholar 

  107. Satoh T et al (2010) LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci USA 107(4):1512–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Childs KS, Randall RE, Goodbourn S (2013) LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA. PLoS ONE 8(5):e64202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bruns AM et al (2014) The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly. Mol Cell 55(5):771–781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Li X et al (2009) The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA. J Biol Chem 284(20):13881–13891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Kato H, Takahasi K, Fujita T (2011) RIG-I-like receptors: cytoplasmic sensors for non-self RNA. Immunol Rev 243(1):91–98

    Article  PubMed  Google Scholar 

  112. Wilkins C, Gale M Jr (2010) Recognition of viruses by cytoplasmic sensors. Curr Opin Immunol 22(1):41–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Takahasi K et al (2009) Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. J Biol Chem 284(26):17465–17474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Li X et al (2009) Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5. Arch Biochem Biophys 488(1):23–33

    Article  CAS  PubMed  Google Scholar 

  115. Takeuchi O, Akira S (2009) Innate immunity to virus infection. Immunol Rev 227(1):75–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yoneyama M et al (2015) Viral RNA detection by RIG-I-like receptors. Curr Opin Immunol 32:48–53

    Article  CAS  PubMed  Google Scholar 

  117. Dickens LS et al (2012) The ‘complexities’ of life and death: death receptor signalling platforms. Exp Cell Res 318(11):1269–1277

    Article  CAS  PubMed  Google Scholar 

  118. Reubold TF, Eschenburg S (2012) A molecular view on signal transduction by the apoptosome. Cell Signal 24(7):1420–1425

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

X.F is funded by the National Natural Science Fund for Young Scholars (Grant No.: 31800639) and the Fundamental Research Funds for the Central Universities (Grant No.:WK2070000110). T.J. is supported by the 100 Talents Program of CAS and National Natural Science Fund (Grant No.: U1732109 and 31870731) and the Fundamental Research Funds for the Central Universities (Grant No.: WK2070000108). We thank Hylamariam Mihiretie Mengist and Ayesha Zahid for proofreading the chapter.

Author information

Authors and Affiliations

  1. Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China

    Xiaojiao Fan & Tengchuan Jin

Authors
  1. Xiaojiao Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tengchuan Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tengchuan Jin .

Editor information

Editors and Affiliations

  1. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China

    Tengchuan Jin

  2. Department of Biological Science, Florida State University, Tallahassee, FL, USA

    Qian Yin

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Fan, X., Jin, T. (2019). Structures of RIG-I-Like Receptors and Insights into Viral RNA Sensing. In: Jin, T., Yin, Q. (eds) Structural Immunology. Advances in Experimental Medicine and Biology, vol 1172. Springer, Singapore. https://doi.org/10.1007/978-981-13-9367-9_8

Download citation

Publish with us

Policies and ethics

Search

Navigation