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Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands.

Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T
Science 339 1426-9 (2013)
Related entries: 3w3g, 3w3j, 3w3k, 3w3l, 3w3n

Cited: 187 times
EuropePMC logo PMID: 23520111

Abstract

Toll-like receptor 7 (TLR7) and TLR8 recognize single-stranded RNA and initiate innate immune responses. Several synthetic agonists of TLR7-TLR8 display novel therapeutic potential; however, the molecular basis for ligand recognition and activation of signaling by TLR7 or TLR8 is largely unknown. In this study, the crystal structures of unliganded and ligand-induced activated human TLR8 dimers were elucidated. Ligand recognition was mediated by a dimerization interface formed by two protomers. Upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity. The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization. Thus, ligand binding induces reorganization of the TLR8 dimer, which enables downstream signaling processes.

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  2. Targeting the innate immune receptor TLR8 using small-molecule agents. Sakaniwa K, Shimizu T. Acta Crystallogr D Struct Biol 76 621-629 (2020)
  3. 50 Years of structural immunology. Wilson IA, Stanfield RL. J Biol Chem 296 100745 (2021)

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  1. Immunoinformatics-guided designing of epitope-based subunit vaccines against the SARS Coronavirus-2 (SARS-CoV-2). Sarkar B, Ullah MA, Johora FT, Taniya MA, Araf Y. Immunobiology 225 151955 (2020)
  2. Designing a next generation multi-epitope based peptide vaccine candidate against SARS-CoV-2 using computational approaches. Saha R, Ghosh P, Burra VLSP. 3 Biotech 11 47 (2021)
  3. Immunoinformatics-guided designing and in silico analysis of epitope-based polyvalent vaccines against multiple strains of human coronavirus (HCoV). Sarkar B, Ullah MA, Araf Y, Islam NN, Zohora US. Expert Rev Vaccines 21 1851-1871 (2022)
  4. Engineering a novel subunit vaccine against SARS-CoV-2 by exploring immunoinformatics approach. Sarkar B, Ullah MA, Araf Y, Rahman MS. Inform Med Unlocked 21 100478 (2020)
  5. Interaction of TLR4 and TLR8 in the Innate Immune Response against Mycobacterium Tuberculosis. Thada S, Horvath GL, Müller MM, Dittrich N, Conrad ML, Sur S, Hussain A, Pelka K, Gaddam SL, Latz E, Slevogt H, Schumann RR, Burkert S. Int J Mol Sci 22 1560 (2021)
  6. In silico approach to design a multi-epitopic vaccine candidate targeting the non-mutational immunogenic regions in envelope protein and surface glycoprotein of SARS-CoV-2. Susithra Priyadarshni M, Isaac Kirubakaran S, Harish MC. J Biomol Struct Dyn 40 12948-12963 (2022)
  7. An in silico approach to study the role of epitope order in the multi-epitope-based peptide (MEBP) vaccine design. Salaikumaran MR, Kasamuthu PS, Aathmanathan VS, Burra VLSP. Sci Rep 12 12584 (2022)
  8. Identification of vaccine targets & design of vaccine against SARS-CoV-2 coronavirus using computational and deep learning-based approaches. Abbasi BA, Saraf D, Sharma T, Sinha R, Singh S, Sood S, Gupta P, Gupta A, Mishra K, Kumari P, Rawal K. PeerJ 10 e13380 (2022)
  9. Immunoinformatics Approach to Design Novel Subunit Vaccine against the Epstein-Barr Virus. Moin AT, Patil RB, Tabassum T, Araf Y, Ullah MA, Snigdha HJ, Alam T, Alvey SA, Rudra B, Mina SA, Akter Y, Zhai J, Zheng C. Microbiol Spectr 10 e0115122 (2022)
  10. Insight into the first multi-epitope-based peptide subunit vaccine against avian influenza A virus (H5N6): An immunoinformatics approach. Mia MM, Hasan M, Ahmed S, Rahman MN. Infect Genet Evol 104 105355 (2022)
  11. Super Secondary Structure Consisting of a Polyproline II Helix and a β-Turn in Leucine Rich Repeats in Bacterial Type III Secretion System Effectors. Batkhishig D, Bilguun K, Enkhbayar P, Miyashita H, Kretsinger RH, Matsushima N. Protein J. 37 223-236 (2018)


Reviews citing this publication (68)

  1. Toll-like receptor signaling pathways. Kawasaki T, Kawai T. Front Immunol 5 461 (2014)
  2. MyD88: a central player in innate immune signaling. Deguine J, Barton GM. F1000Prime Rep 6 97 (2014)
  3. Assembly and localization of Toll-like receptor signalling complexes. Gay NJ, Symmons MF, Gangloff M, Bryant CE. Nat. Rev. Immunol. 14 546-558 (2014)
  4. Recognition of lipopolysaccharide pattern by TLR4 complexes. Park BS, Lee JO. Exp. Mol. Med. 45 e66 (2013)
  5. Microbial sensing by Toll-like receptors and intracellular nucleic acid sensors. Pandey S, Kawai T, Akira S. Cold Spring Harb Perspect Biol 7 a016246 (2014)
  6. Toll-like receptors: Activation, signalling and transcriptional modulation. De Nardo D. Cytokine 74 181-189 (2015)
  7. The critical role of toll-like receptors--From microbial recognition to autoimmunity: A comprehensive review. Jiménez-Dalmaroni MJ, Gerswhin ME, Adamopoulos IE. Autoimmun Rev 15 1-8 (2016)
  8. TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens. McClure R, Massari P. Front Immunol 5 386 (2014)
  9. Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions and immune responses. Rauta PR, Samanta M, Dash HR, Nayak B, Das S. Immunol. Lett. 158 14-24 (2014)
  10. Toll-like receptors: the swiss army knife of immunity and vaccine development. Dowling JK, Mansell A. Clin Transl Immunology 5 e85 (2016)
  11. Trafficking of endosomal Toll-like receptors. Lee BL, Barton GM. Trends Cell Biol. 24 360-369 (2014)
  12. Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology. Mahla RS, Mahla RS, Reddy MC, Prasad DV, Kumar H. Front Immunol 4 248 (2013)
  13. Toll-like Receptors in the Vascular System: Sensing the Dangers Within. Goulopoulou S, McCarthy CG, Webb RC. Pharmacol. Rev. 68 142-167 (2016)
  14. Distinct and Orchestrated Functions of RNA Sensors in Innate Immunity. Liu G, Gack MU. Immunity 53 26-42 (2020)
  15. Structural biology of innate immunity. Yin Q, Fu TM, Li J, Wu H. Annu. Rev. Immunol. 33 393-416 (2015)
  16. Toll-like Receptor Agonist Conjugation: A Chemical Perspective. Ignacio BJ, Albin TJ, Esser-Kahn AP, Verdoes M. Bioconjug Chem 29 587-603 (2018)
  17. RNA sensors of the innate immune system and their detection of pathogens. Chen N, Xia P, Li S, Zhang T, Wang TT, Zhu J. IUBMB Life 69 297-304 (2017)
  18. Advances in Toll-like receptor biology: Modes of activation by diverse stimuli. Bryant CE, Gay NJ, Heymans S, Sacre S, Schaefer L, Midwood KS. Crit. Rev. Biochem. Mol. Biol. 50 359-379 (2015)
  19. Toll-like receptor signalling through macromolecular protein complexes. Bryant CE, Symmons M, Gay NJ. Mol. Immunol. 63 162-165 (2015)
  20. The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways. Vajjhala PR, Ve T, Bentham A, Stacey KJ, Kobe B. Mol. Immunol. 86 23-37 (2017)
  21. Nucleic acid-sensing TLRs and autoimmunity: novel insights from structural and cell biology. Pelka K, Shibata T, Miyake K, Latz E. Immunol. Rev. 269 60-75 (2016)
  22. Toll-like receptor agonists: a patent review (2011 - 2013). Hussein WM, Liu TY, Skwarczynski M, Toth I. Expert Opin Ther Pat 24 453-470 (2014)
  23. Drugging Membrane Protein Interactions. Yin H, Flynn AD. Annu Rev Biomed Eng 18 51-76 (2016)
  24. Structure and function of toll-like receptor 8. Ohto U, Tanji H, Shimizu T. Microbes Infect. 16 273-282 (2014)
  25. Toll-Like Receptors: General Molecular and Structural Biology. Behzadi P, García-Perdomo HA, Karpiński TM. J Immunol Res 2021 9914854 (2021)
  26. Directing the immune system with chemical compounds. Mancini RJ, Stutts L, Ryu KA, Tom JK, Esser-Kahn AP. ACS Chem. Biol. 9 1075-1085 (2014)
  27. International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease. Bryant CE, Orr S, Ferguson B, Symmons MF, Boyle JP, Monie TP. Pharmacol. Rev. 67 462-504 (2015)
  28. Distinct roles of TNF-related apoptosis-inducing ligand (TRAIL) in viral and bacterial infections: from pathogenesis to pathogen clearance. Gyurkovska V, Ivanovska N. Inflamm. Res. 65 427-437 (2016)
  29. Molecular and Structural Basis of DNA Sensors in Antiviral Innate Immunity. Zahid A, Ismail H, Li B, Jin T. Front Immunol 11 613039 (2020)
  30. Recent progress in the development of Toll-like receptor (TLR) antagonists. Patra MC, Choi S. Expert Opin Ther Pat 26 719-730 (2016)
  31. Activation of toll-like receptor signaling pathways leading to nitric oxide-mediated antiviral responses. Abdul-Cader MS, Amarasinghe A, Abdul-Careem MF. Arch. Virol. 161 2075-2086 (2016)
  32. Discrimination Between Self and Non-Self-Nucleic Acids by the Innate Immune System. Kawasaki T, Kawai T. Int Rev Cell Mol Biol 344 1-30 (2019)
  33. Nucleic acid-sensing TLRs: trafficking and regulation. Majer O, Liu B, Barton GM. Curr. Opin. Immunol. 44 26-33 (2017)
  34. The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome. Petes C, Odoardi N, Gee K. Front Immunol 8 1075 (2017)
  35. Lipoteichoic acids as a major virulence factor causing inflammatory responses via Toll-like receptor 2. Kang SS, Sim JR, Yun CH, Han SH. Arch. Pharm. Res. 39 1519-1529 (2016)
  36. Regulation of the nucleic acid-sensing Toll-like receptors. Lind NA, Rael VE, Pestal K, Liu B, Barton GM. Nat Rev Immunol 22 224-235 (2022)
  37. Toll-like receptors and their role in persistent pain. Lacagnina MJ, Watkins LR, Grace PM. Pharmacol. Ther. 184 145-158 (2018)
  38. Structures and recognition modes of toll-like receptors. Gao D, Li W. Proteins 85 3-9 (2017)
  39. Structures of pattern recognition receptors reveal molecular mechanisms of autoinhibition, ligand recognition and oligomerization. Chuenchor W, Jin T, Ravilious G, Xiao TS. Curr. Opin. Immunol. 26 14-20 (2014)
  40. Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases. Cannova J, Breslin S J P, Zhang J. Front Med 9 288-303 (2015)
  41. Recent advances in glycoprotein production for structural biology: toward tailored design of glycoforms. Kamiya Y, Satoh T, Kato K. Curr. Opin. Struct. Biol. 26 44-53 (2014)
  42. TLR7 Structure: Cut in Z-Loop. Maeda K, Akira S. Immunity 45 705-707 (2016)
  43. Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019. Dai J, Wang Y, Wang H, Gao Z, Wang Y, Fang M, Shi S, Zhang P, Wang H, Su Y, Yang M. Front Microbiol 13 948770 (2022)
  44. Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants. Bhagchandani S, Johnson JA, Irvine DJ. Adv Drug Deliv Rev 175 113803 (2021)
  45. Strategies for designing synthetic immune agonists. Wu TY. Immunology 148 315-325 (2016)
  46. Structural aspects of nucleic acid-sensing Toll-like receptors. Ohto U, Shimizu T. Biophys Rev 8 33-43 (2016)
  47. Toward a structural understanding of nucleic acid-sensing Toll-like receptors in the innate immune system. Zhang Z, Ohto U, Shimizu T. FEBS Lett. 591 3167-3181 (2017)
  48. Chemical Tools for Studying TLR Signaling Dynamics. Oosenbrug T, van de Graaff MJ, Ressing ME, van Kasteren SI. Cell Chem Biol 24 801-812 (2017)
  49. Virtual Screening Approaches towards the Discovery of Toll-Like Receptor Modulators. Pérez-Regidor L, Zarioh M, Ortega L, Martín-Santamaría S. Int J Mol Sci 17 (2016)
  50. Balancing Inflammation: Computational Design of Small-Molecule Toll-like Receptor Modulators. Murgueitio MS, Rakers C, Frank A, Wolber G. Trends Pharmacol. Sci. 38 155-168 (2017)
  51. Mechanisms controlling nucleic acid-sensing Toll-like receptors. Miyake K, Shibata T, Ohto U, Shimizu T, Saitoh SI, Fukui R, Murakami Y. Int. Immunol. 30 43-51 (2018)
  52. Structural insights into ligand recognition and regulation of nucleic acid-sensing Toll-like receptors. Shimizu T. Curr. Opin. Struct. Biol. 47 52-59 (2017)
  53. The potential role of retroviruses in autoimmunity. Yu P. Immunol. Rev. 269 85-99 (2016)
  54. Toll-Like Receptor 4 and Inflammatory Micro-Environment of Pancreatic Islets in Type-2 Diabetes Mellitus: A Therapeutic Perspective. Wang Z, Ni X, Zhang L, Sun L, Zhu X, Zhou Q, Yang Z, Yuan H. Diabetes Metab Syndr Obes 13 4261-4272 (2020)
  55. Comparative Geometrical Analysis of Leucine-Rich Repeat Structures in the Nod-Like and Toll-Like Receptors in Vertebrate Innate Immunity. Matsushima N, Miyashita H, Enkhbayar P, Kretsinger RH. Biomolecules 5 1955-1978 (2015)
  56. Recent clinical trends in Toll-like receptor targeting therapeutics. Anwar MA, Shah M, Kim J, Choi S. Med Res Rev 39 1053-1090 (2019)
  57. Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles. Kaushik D, Kaur A, Petrovsky N, Salunke DB. RSC Med Chem 12 1065-1120 (2021)
  58. Surface toll-like receptor 9 on immune cells and its immunomodulatory effect. Kou M, Wang L. Front Immunol 14 1259989 (2023)
  59. Targeting toll-like receptor 7/8 for immunotherapy: recent advances and prospectives. Sun H, Li Y, Zhang P, Xing H, Zhao S, Song Y, Wan D, Yu J. Biomark Res 10 89 (2022)
  60. Toll-like receptor-guided therapeutic intervention of human cancers: molecular and immunological perspectives. Mukherjee S, Patra R, Behzadi P, Masotti A, Paolini A, Sarshar M. Front Immunol 14 1244345 (2023)
  61. Cell Surface Expression of Endosomal Toll-Like Receptors-A Necessity or a Superfluous Duplication? Mielcarska MB, Bossowska-Nowicka M, Toka FN. Front Immunol 11 620972 (2020)
  62. Host-pathogen protein-nucleic acid interactions: A comprehensive review. Jain A, Mittal S, Tripathi LP, Nussinov R, Ahmad S. Comput Struct Biotechnol J 20 4415-4436 (2022)
  63. Inhibition of RNA-binding proteins with small molecules. Wu P. Nat Rev Chem 4 441-458 (2020)
  64. Innate Immune Sensing of Influenza A Virus. Malik G, Zhou Y. Viruses 12 (2020)
  65. RNA is taking its Toll: Impact of RNA-specific Toll-like receptors on health and disease. Vierbuchen T, Stein K, Heine H. Allergy 74 223-235 (2019)
  66. Small molecule modulators of immune pattern recognition receptors. Tsukidate T, Hespen CW, Hang HC. RSC Chem Biol 4 1014-1036 (2023)
  67. Sources of Pathogenic Nucleic Acids in Systemic Lupus Erythematosus. Mustelin T, Lood C, Giltiay NV. Front Immunol 10 1028 (2019)
  68. [Structural Analyses of Toll-like Receptor Sensing Single-stranded Nucleic Acids and Its Application]. Shimizu T. Yakugaku Zasshi 136 173-178 (2016)

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  2. Toll-like receptor 8 senses degradation products of single-stranded RNA. Tanji H, Ohto U, Shibata T, Taoka M, Yamauchi Y, Isobe T, Miyake K, Shimizu T. Nat. Struct. Mol. Biol. 22 109-115 (2015)
  3. Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor for Guanosine and Single-Stranded RNA. Zhang Z, Ohto U, Shibata T, Krayukhina E, Taoka M, Yamauchi Y, Tanji H, Isobe T, Uchiyama S, Miyake K, Shimizu T. Immunity 45 737-748 (2016)
  4. Endosomal localization of TLR8 confers distinctive proteolytic processing on human myeloid cells. Ishii N, Funami K, Tatematsu M, Seya T, Matsumoto M. J Immunol 193 5118-5128 (2014)
  5. Human TLR8 is activated upon recognition of Borrelia burgdorferi RNA in the phagosome of human monocytes. Cervantes JL, La Vake CJ, Weinerman B, Luu S, O'Connell C, Verardi PH, Salazar JC. J. Leukoc. Biol. 94 1231-1241 (2013)
  6. Roles of the cleaved N-terminal TLR3 fragment and cell surface TLR3 in double-stranded RNA sensing. Murakami Y, Fukui R, Motoi Y, Kanno A, Shibata T, Tanimura N, Saitoh S, Miyake K. J Immunol 193 5208-5217 (2014)
  7. Novel HIV-1 miRNAs stimulate TNFα release in human macrophages via TLR8 signaling pathway. Bernard MA, Zhao H, Yue SC, Anandaiah A, Koziel H, Tachado SD. PLoS ONE 9 e106006 (2014)
  8. Structural analysis reveals TLR7 dynamics underlying antagonism. Tojo S, Zhang Z, Matsui H, Tahara M, Ikeguchi M, Kochi M, Kamada M, Shigematsu H, Tsutsumi A, Adachi N, Shibata T, Yamamoto M, Kikkawa M, Senda T, Isobe Y, Ohto U, Shimizu T. Nat Commun 11 5204 (2020)
  9. The structural basis for endotoxin-induced allosteric regulation of the Toll-like receptor 4 (TLR4) innate immune receptor. Paramo T, Piggot TJ, Bryant CE, Bond PJ. J. Biol. Chem. 288 36215-36225 (2013)
  10. Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. Kanno A, Tanimura N, Ishizaki M, Ohko K, Motoi Y, Onji M, Fukui R, Shimozato T, Yamamoto K, Shibata T, Sano S, Sugahara-Tobinai A, Takai T, Ohto U, Shimizu T, Saitoh S, Miyake K. Nat Commun 6 6119 (2015)
  11. Guanosine and its modified derivatives are endogenous ligands for TLR7. Shibata T, Ohto U, Nomura S, Kibata K, Motoi Y, Zhang Y, Murakami Y, Fukui R, Ishimoto T, Sano S, Ito T, Shimizu T, Miyake K. Int. Immunol. 28 211-222 (2016)
  12. RNA and imidazoquinolines are sensed by distinct TLR7/8 ectodomain sites resulting in functionally disparate signaling events. Colak E, Leslie A, Zausmer K, Khatamzas E, Kubarenko AV, Pichulik T, Klimosch SN, Mayer A, Siggs O, Hector A, Fischer R, Klesser B, Rautanen A, Frank M, Hill AV, Manoury B, Beutler B, Hartl D, Simmons A, Weber AN. J. Immunol. 192 5963-5973 (2014)
  13. Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13. Song W, Wang J, Han Z, Zhang Y, Zhang H, Wang W, Chang J, Xia B, Fan S, Zhang D, Wang J, Wang HW, Chai J. Nat. Struct. Mol. Biol. 22 782-787 (2015)
  14. Structure-based design of novel human Toll-like receptor 8 agonists. Kokatla HP, Sil D, Tanji H, Ohto U, Malladi SS, Fox LM, Shimizu T, David SA. ChemMedChem 9 719-723 (2014)
  15. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses. Dowling DJ, Scott EA, Scheid A, Bergelson I, Joshi S, Pietrasanta C, Brightman S, Sanchez-Schmitz G, Van Haren SD, Ninković J, Kats D, Guiducci C, de Titta A, Bonner DK, Hirosue S, Swartz MA, Hubbell JA, Levy O. J. Allergy Clin. Immunol. 140 1339-1350 (2017)
  16. Exquisite selectivity for human toll-like receptor 8 in substituted furo[2,3-c]quinolines. Kokatla HP, Sil D, Malladi SS, Balakrishna R, Hermanson AR, Fox LM, Wang X, Dixit A, David SA. J. Med. Chem. 56 6871-6885 (2013)
  17. Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses. Ugolini M, Gerhard J, Burkert S, Jensen KJ, Georg P, Ebner F, Volkers SM, Thada S, Dietert K, Bauer L, Schäfer A, Helbig ET, Opitz B, Kurth F, Sur S, Dittrich N, Gaddam S, Conrad ML, Benn CS, Blohm U, Gruber AD, Hutloff A, Hartmann S, Boekschoten MV, Müller M, Jungersen G, Schumann RR, Suttorp N, Sander LE. Nat. Immunol. 19 386-396 (2018)
  18. Determinants of activity at human Toll-like receptors 7 and 8: quantitative structure-activity relationship (QSAR) of diverse heterocyclic scaffolds. Yoo E, Salunke DB, Sil D, Guo X, Salyer AC, Hermanson AR, Kumar M, Malladi SS, Balakrishna R, Thompson WH, Tanji H, Ohto U, Shimizu T, David SA. J. Med. Chem. 57 7955-7970 (2014)
  19. Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity. Xu L, Xiang J, Liu Y, Xu J, Luo Y, Feng L, Liu Z, Peng R. Nanoscale 8 3785-3795 (2016)
  20. Stimulation of innate immune cells by light-activated TLR7/8 agonists. Ryu KA, Stutts L, Tom JK, Mancini RJ, Esser-Kahn AP. J. Am. Chem. Soc. 136 10823-10825 (2014)
  21. Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity. Beesu M, Caruso G, Salyer AC, Khetani KK, Sil D, Weerasinghe M, Tanji H, Ohto U, Shimizu T, David SA. J. Med. Chem. 58 7833-7849 (2015)
  22. Letter A modified dinucleotide motif specifies tRNA recognition by TLR7. Kaiser S, Rimbach K, Eigenbrod T, Dalpke AH, Helm M. RNA 20 1351-1355 (2014)
  23. Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8. Tanji H, Ohto U, Motoi Y, Shibata T, Miyake K, Shimizu T. Proc. Natl. Acad. Sci. U.S.A. 113 3012-3017 (2016)
  24. Covalently coupled immunostimulant heterodimers. Mancini RJ, Tom JK, Esser-Kahn AP. Angew. Chem. Int. Ed. Engl. 53 189-192 (2014)
  25. RIG-I and Other RNA Sensors in Antiviral Immunity. Chow KT, Gale M, Loo YM. Annu. Rev. Immunol. 36 667-694 (2018)
  26. TLR8 gene polymorphism and association in bacterial load in southern Punjab of Pakistan: an association study with pulmonary tuberculosis. Bukhari M, Aslam MA, Khan A, Iram Q, Akbar A, Naz AG, Ahmad S, Ahmad MM, Ashfaq UA, Aziz H, Ali M. Int. J. Immunogenet. 42 46-51 (2015)
  27. The Imidazoquinoline Toll-Like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes. Ganapathi L, Van Haren S, Dowling DJ, Bergelson I, Shukla NM, Malladi SS, Balakrishna R, Tanji H, Ohto U, Shimizu T, David SA, Levy O. PLoS ONE 10 e0134640 (2015)
  28. The Processed Amino-Terminal Fragment of Human TLR7 Acts as a Chaperone To Direct Human TLR7 into Endosomes. Hipp MM, Shepherd D, Booth S, Waithe D, Reis e Sousa C, Cerundolo V. J. Immunol. 194 5417-5425 (2015)
  29. HIV-derived ssRNA binds to TLR8 to induce inflammation-driven macrophage foam cell formation. Bernard MA, Han X, Inderbitzin S, Agbim I, Zhao H, Koziel H, Tachado SD. PLoS ONE 9 e104039 (2014)
  30. Human Toll-like receptor 8-selective agonistic activities in 1-alkyl-1H-benzimidazol-2-amines. Beesu M, Malladi SS, Fox LM, Jones CD, Dixit A, David SA. J. Med. Chem. 57 7325-7341 (2014)
  31. The evolution of bat nucleic acid-sensing Toll-like receptors. Escalera-Zamudio M, Zepeda-Mendoza ML, Loza-Rubio E, Rojas-Anaya E, Méndez-Ojeda ML, Arias CF, Greenwood AD. Mol. Ecol. 24 5899-5909 (2015)
  32. Base modification strategies to modulate immune stimulation by an siRNA. Valenzuela RA, Suter SR, Ball-Jones AA, Ibarra-Soza JM, Zheng Y, Beal PA. Chembiochem 16 262-267 (2015)
  33. GlycoMinestruct: a new bioinformatics tool for highly accurate mapping of the human N-linked and O-linked glycoproteomes by incorporating structural features. Li F, Li C, Revote J, Zhang Y, Webb GI, Li J, Song J, Lithgow T. Sci Rep 6 34595 (2016)
  34. HCV-infected cells and differentiation increase monocyte immunoregulatory galectin-9 production. Harwood NM, Golden-Mason L, Cheng L, Rosen HR, Mengshol JA. J. Leukoc. Biol. 99 495-503 (2016)
  35. Structure Based Modeling of Small Molecules Binding to the TLR7 by Atomistic Level Simulations. Gentile F, Deriu MA, Licandro G, Prunotto A, Danani A, Tuszynski JA. Molecules 20 8316-8340 (2015)
  36. Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity. Parthier C, Stelter M, Ursel C, Fandrich U, Lilie H, Breithaupt C, Stubbs MT. Proc. Natl. Acad. Sci. U.S.A. 111 6281-6286 (2014)
  37. Toll-Like Receptor 11 (TLR11) Interacts with Flagellin and Profilin through Disparate Mechanisms. Hatai H, Lepelley A, Zeng W, Hayden MS, Ghosh S. PLoS ONE 11 e0148987 (2016)
  38. Adaptive Evolution of Toll-Like Receptors (TLRs) in the Family Suidae. Darfour-Oduro KA, Megens HJ, Roca AL, Groenen MA, Schook LB. PLoS ONE 10 e0124069 (2015)
  39. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Ackerman SE, Pearson CI, Gregorio JD, Gonzalez JC, Kenkel JA, Hartmann FJ, Luo A, Ho PY, LeBlanc H, Blum LK, Kimmey SC, Luo A, Nguyen ML, Paik JC, Sheu LY, Ackerman B, Lee A, Li H, Melrose J, Laura RP, Ramani VC, Henning KA, Jackson DY, Safina BS, Yonehiro G, Devens BH, Carmi Y, Chapin SJ, Bendall SC, Kowanetz M, Dornan D, Engleman EG, Alonso MN. Nat Cancer 2 18-33 (2021)
  40. Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function. Aluri J, Bach A, Kaviany S, Chiquetto Paracatu L, Kitcharoensakkul M, Walkiewicz MA, Putnam CD, Shinawi M, Saucier N, Rizzi EM, Harmon MT, Keppel MP, Ritter M, Similuk M, Kulm E, Joyce M, de Jesus AA, Goldbach-Mansky R, Lee YS, Cella M, Kendall PL, Dinauer MC, Bednarski JJ, Bemrich-Stolz C, Canna SW, Abraham SM, Demczko MM, Powell J, Jones SM, Scurlock AM, De Ravin SS, Bleesing JJ, Connelly JA, Rao VK, Schuettpelz LG, Cooper MA. Blood 137 2450-2462 (2021)
  41. Synergistic activation of Toll-like receptor 8 by two RNA degradation products. Geyer M, Pelka K, Latz E. Nat. Struct. Mol. Biol. 22 99-101 (2015)
  42. Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub. Latty SL, Sakai J, Hopkins L, Verstak B, Paramo T, Berglund NA, Cammarota E, Cicuta P, Gay NJ, Bond PJ, Klenerman D, Bryant CE. Elife 7 (2018)
  43. Adaptive evolution of virus-sensing toll-like receptor 8 in bats. Schad J, Voigt CC. Immunogenetics 68 783-795 (2016)
  44. Discovery of Potent and Orally Bioavailable Small Molecule Antagonists of Toll-like Receptors 7/8/9 (TLR7/8/9). Mussari CP, Dodd DS, Sreekantha RK, Pasunoori L, Wan H, Posy SL, Critton D, Ruepp S, Subramanian M, Watson A, Davies P, Schieven GL, Salter-Cid LM, Srivastava R, Tagore DM, Dudhgaonkar S, Poss MA, Carter PH, Dyckman AJ. ACS Med Chem Lett 11 1751-1758 (2020)
  45. Homology and molecular dynamics models of toll-like receptor 7 protein and its dimerization. Tseng CY, Gajewski M, Danani A, Tuszynski JA. Chem Biol Drug Des 83 656-665 (2014)
  46. Molecular Determinants of GS-9620-Dependent TLR7 Activation. Rebbapragada I, Birkus G, Perry J, Xing W, Kwon H, Pflanz S. PLoS ONE 11 e0146835 (2016)
  47. Selectivity of Human TLR9 for Double CpG Motifs and Implications for the Recognition of Genomic DNA. Pohar J, Yamamoto C, Fukui R, Cajnko MM, Miyake K, Jerala R, Benčina M. J. Immunol. 198 2093-2104 (2017)
  48. Small-molecule inhibition of TLR8 through stabilization of its resting state. Zhang S, Hu Z, Tanji H, Jiang S, Das N, Li J, Sakaniwa K, Jin J, Bian Y, Ohto U, Shimizu T, Yin H. Nat. Chem. Biol. 14 58-64 (2018)
  49. TLR7/8 agonists activate a mild immune response in rabbits through TLR8 but not TLR7. Lai CY, Liu YL, Yu GY, Maa MC, Leu TH, Xu C, Luo Y, Xiang R, Chuang TH. Vaccine 32 5593-5599 (2014)
  50. A single naturally occurring 2'-O-methylation converts a TLR7- and TLR8-activating RNA into a TLR8-specific ligand. Jung S, von Thülen T, Laukemper V, Pigisch S, Hangel D, Wagner H, Kaufmann A, Bauer S. PLoS ONE 10 e0120498 (2015)
  51. Crystal structure of the C-terminal domain of mouse TLR9. Collins B, Wilson IA. Proteins 82 2874-2878 (2014)
  52. Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses. Chuang TH, Lai CY, Tseng PH, Yuan CJ, Hsu LC. PLoS ONE 9 e108808 (2014)
  53. Identification and characterization of toll-like receptors (TLRs) in the Chinese tree shrew (Tupaia belangeri chinensis). Yu D, Wu Y, Xu L, Fan Y, Peng L, Xu M, Yao YG. Dev. Comp. Immunol. 60 127-138 (2016)
  54. Identification of a Potential mRNA-based Vaccine Candidate against the SARS-CoV-2 Spike Glycoprotein: A Reverse Vaccinology Approach. Durojaye OA, Sedzro DM, Idris MO, Yekeen AA, Fadahunsi AA, Alakanse OS. ChemistrySelect 7 e202103903 (2022)
  55. Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9. Pohar J, Lainšček D, Ivičak-Kocjan K, Cajnko MM, Jerala R, Benčina M. Nat Commun 8 15363 (2017)
  56. Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives. Bazin HG, Li Y, Khalaf JK, Mwakwari S, Livesay MT, Evans JT, Johnson DA. Bioorg. Med. Chem. Lett. 25 1318-1323 (2015)
  57. TLR8 activation and inhibition by guanosine analogs in RNA: Importance of functional groups and chain length. Hu T, Suter SR, Mumbleau MM, Beal PA. Bioorg. Med. Chem. 26 77-83 (2018)
  58. TLR8 and its endogenous ligand miR-21 contribute to neuropathic pain in murine DRG. Zhang ZJ, Guo JS, Li SS, Wu XB, Cao DL, Jiang BC, Jing PB, Bai XQ, Li CH, Wu ZH, Lu Y, Gao YJ. J. Exp. Med. 215 3019-3037 (2018)
  59. Computational Insight Into the Structural Organization of Full-Length Toll-Like Receptor 4 Dimer in a Model Phospholipid Bilayer. Patra MC, Kwon HK, Batool M, Choi S. Front Immunol 9 489 (2018)
  60. Conformational Sampling and Binding Site Assessment of Suppression of Tumorigenicity 2 Ectodomain. Yang CY, Delproposto J, Chinnaswamy K, Brown WC, Wang S, Stuckey JA, Wang X. PLoS ONE 11 e0146522 (2016)
  61. Cytidine deaminase enables Toll-like receptor 8 activation by cytidine or its analogs. Furusho K, Shibata T, Sato R, Fukui R, Motoi Y, Zhang Y, Saitoh SI, Ichinohe T, Moriyama M, Nakamura S, Miyake K. Int Immunol 31 167-173 (2019)
  62. Enrichment assessment of multiple virtual screening strategies for Toll-like receptor 8 agonists based on a maximal unbiased benchmarking data set. Pei F, Jin H, Zhou X, Xia J, Sun L, Liu Z, Zhang L. Chem Biol Drug Des 86 1226-1241 (2015)
  63. Selective evolution of Toll-like receptors 3, 7, 8, and 9 in bats. Jiang H, Li J, Li L, Zhang X, Yuan L, Chen J. Immunogenetics 69 271-285 (2017)
  64. Cyprinid-specific duplicated membrane TLR5 senses dsRNA as functional homodimeric receptors. Liao Z, Yang C, Jiang R, Zhu W, Zhang Y, Su J. EMBO Rep 23 e54281 (2022)
  65. Direct Toll-Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies. Chatillon JF, Hamieh M, Bayeux F, Abasq C, Fauquembergue E, Drouet A, Guisier F, Latouche JB, Musette P. Immun Inflamm Dis 3 1-13 (2015)
  66. Duplicated TLR5 of zebrafish functions as a heterodimeric receptor. Voogdt CGP, Wagenaar JA, van Putten JPM. Proc. Natl. Acad. Sci. U.S.A. 115 E3221-E3229 (2018)
  67. In silico analysis of human Toll-like receptor 7 ligand binding domain. Gupta CL, Akhtar S, Sayyed U, Pathak N, Bajpai P. Biotechnol. Appl. Biochem. 63 441-450 (2016)
  68. Inhibitory Effects of Dietary N-Glycans From Bovine Lactoferrin on Toll-Like Receptor 8; Comparing Efficacy With Chloroquine. Figueroa-Lozano S, Valk-Weeber RL, Akkerman R, Abdulahad W, van Leeuwen SS, Dijkhuizen L, de Vos P. Front Immunol 11 790 (2020)
  69. Titer estimation for quality control (TEQC) method: A practical approach for optimal production of protein complexes using the baculovirus expression vector system. Imasaki T, Wenzel S, Yamada K, Bryant ML, Takagi Y. PLoS ONE 13 e0195356 (2018)
  70. Toll-like receptor 2 antagonists identified through virtual screening and experimental validation. Durai P, Shin HJ, Achek A, Kwon HK, Govindaraj RG, Panneerselvam S, Yesudhas D, Choi J, No KT, Choi S. FEBS J. 284 2264-2283 (2017)
  71. Inhibition of human macrophage activation via pregnane neurosteroid interactions with toll-like receptors: Sex differences and structural requirements. Balan I, Aurelian L, Williams KS, Campbell B, Meeker RB, Morrow AL. Front Immunol 13 940095 (2022)
  72. Kinetics reshape antitumor immunity: Timing, duration, and combination are of importance for successful cancer immunotherapy. Jin SM, Yoo YJ, Lim YT. Clin Transl Med 13 e1420 (2023)
  73. Molecular docking of SARS-COV-2 Spike epitope sequences identifies heterodimeric peptide-protein complex formation with human Zo-1, TLR8 and brain specific glial proteins. Dasgupta S, Bandyopadhyay M. Med Hypotheses 157 110706 (2021)
  74. Purifying selection and concerted evolution of RNA-sensing toll-like receptors in migratory waders. Raven N, Lisovski S, Klaassen M, Lo N, Madsen T, Ho SYW, Ujvari B. Infect. Genet. Evol. 53 135-145 (2017)
  75. TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling. Peña OA, Lubin A, Hockings C, Rowell J, Jung Y, Hoade Y, Dace P, Valdivia LE, Tuschl K, Böiers C, Virgilio MC, Richardson S, Payne EM. Blood Adv 5 4112-4124 (2021)
  76. Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists. Yang Y, Csakai A, Jiang S, Smith C, Tanji H, Huang J, Jones T, Sakaniwa K, Broadwell L, Shi C, Soti S, Ohto U, Fang Y, Shen S, Deng F, Shimizu T, Yin H. Nat Commun 12 4351 (2021)
  77. A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study. Gentile F, Deriu MA, Barakat K, Danani A, Tuszynski J. Pharmaceuticals (Basel) 11 (2018)
  78. A Novel Small-Molecule Inhibitor of Endosomal TLRs Reduces Inflammation and Alleviates Autoimmune Disease Symptoms in Murine Models. Patra MC, Achek A, Kim GY, Panneerselvam S, Shin HJ, Baek WY, Lee WH, Sung J, Jeong U, Cho EY, Kim W, Kim E, Suh CH, Choi S. Cells 9 (2020)
  79. Avian Toll-like receptor allelic diversity far exceeds human polymorphism: an insight from domestic chicken breeds. Świderská Z, Šmídová A, Buchtová L, Bryjová A, Fabiánová A, Munclinger P, Vinkler M. Sci Rep 8 17878 (2018)
  80. DSP-0509, a systemically available TLR7 agonist, exhibits combination effect with immune checkpoint blockade by activating anti-tumor immune effects. Ota Y, Nagai Y, Hirose Y, Hori S, Koga-Yamakawa E, Eguchi K, Sumida K, Murata M, Umehara H, Yamamoto S. Front Immunol 14 1055671 (2023)
  81. Design and Synthesis of N1-Modified Imidazoquinoline Agonists for Selective Activation of Toll-like Receptors 7 and 8. Larson P, Kucaba TA, Xiong Z, Olin M, Griffith TS, Ferguson DM. ACS Med Chem Lett 8 1148-1152 (2017)
  82. Design of anti-BVDV drug based on common chemical features, their interaction, and scaffolds of TLR8 agonists. Chai HH, Lim D, Suk JE, Choi BH, Cho YM. Int. J. Biol. Macromol. 92 1095-1112 (2016)
  83. Entamoeba histolytica HM-1: IMSS gene expression profiling identifies key hub genes, potential biomarkers, and pathways in Amoebiasis infection: a systematic network meta-analysis. Verma RN, Malik MZ, Subbarao N, Singh GP, Sinha DN. Biosci Rep 42 BSR20220191 (2022)
  84. Evaluation of Toll-Like Receptor 11 Agonist Adjuvant Activity in Immunization of BALB/c Mice with Total Lysate Antigens of Toxoplasma gondii RH Strain. Shokri M, Hazrati Tappeh K, Meshkini E, Aminpour A. Iran J Parasitol 15 349-356 (2020)
  85. Extension and refinement of the recognition motif for Toll-like receptor 5 activation by flagellin. Ivičak-Kocjan K, Forstnerič V, Panter G, Jerala R, Benčina M. J. Leukoc. Biol. 104 767-776 (2018)
  86. Further exploration of the structure-activity relationship of imidazoquinolines; identification of potent C7-substituted imidazoquinolines. Hunt JR, Kleindl PA, Moulder KR, Prisinzano TE, Forrest ML. Bioorg Med Chem Lett 30 126788 (2020)
  87. Imidazoquinolines with improved pharmacokinetic properties induce a high IFNα to TNFα ratio in vitro and in vivo. Keppler M, Straß S, Geiger S, Fischer T, Späth N, Weinstein T, Schwamborn A, Guezguez J, Guse JH, Laufer S, Burnet M. Front Immunol 14 1168252 (2023)
  88. Insights on the mechanism of action of immunostimulants in relation to their pharmacological potency. The effects of imidazoquinolines on TLR8. Kubli-Garfias C, Vázquez-Ramírez R, Trejo-Muñoz C, Berber A. PLoS ONE 12 e0178846 (2017)
  89. Modulation of Toll-like receptor 1 intracellular domain structure and activity by Zn2+ ions. Lushpa VA, Goncharuk MV, Lin C, Zalevsky AO, Talyzina IA, Luginina AP, Vakhrameev DD, Shevtsov MB, Goncharuk SA, Arseniev AS, Borshchevskiy VI, Wang X, Mineev KS. Commun Biol 4 1003 (2021)
  90. Molecular dynamics simulations reveal the selectivity mechanism of structurally similar agonists to TLR7 and TLR8. Wang X, Chen Y, Zhang S, Deng JN. PLoS One 17 e0260565 (2022)
  91. N-glycosylation of UNC93B1 at a Specific Asparagine Residue Is Required for TLR9 Signaling. Song HS, Park S, Huh JW, Lee YR, Jung DJ, Yang C, Kim SH, Kim HM, Kim YM. Front Immunol 13 875083 (2022)
  92. Novel TLR7/8 agonists promote activation of HIV-1 latent reservoirs and human T and NK cells. Li Y, Wang Z, Hou Y, Liu X, Hong J, Shi X, Huang X, Zhang T, Liao X, Zhang L. Front Microbiol 14 1033448 (2023)
  93. Phosphodiester backbone of the CpG motif within immunostimulatory oligodeoxynucleotides augments activation of Toll-like receptor 9. Pohar J, Lainšček D, Kunšek A, Cajnko MM, Jerala R, Benčina M. Sci Rep 7 14598 (2017)
  94. RNA-Based Immunostimulatory Liposomal Spherical Nucleic Acids as Potent TLR7/8 Modulators. Guan C, Chernyak N, Dominguez D, Cole L, Zhang B, Mirkin CA. Small 14 e1803284 (2018)
  95. SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion. Gardiman E, Bianchetto-Aguilera F, Gasperini S, Tiberio L, Scandola M, Lotti V, Gibellini D, Salvi V, Bosisio D, Cassatella MA, Tamassia N. Cells 11 3785 (2022)
  96. Selecting Therapeutic Antisense Oligonucleotides with Gene Targeting and TLR8 Potentiating Bifunctionality. Sapkota S, Gantier MP. Methods Mol Biol 2691 225-234 (2023)
  97. Sensing of HIV-1 by TLR8 activates human T cells and reverses latency. Meås HZ, Haug M, Beckwith MS, Louet C, Ryan L, Hu Z, Landskron J, Nordbø SA, Taskén K, Yin H, Damås JK, Flo TH. Nat Commun 11 147 (2020)
  98. Small-Molecule TLR8 Antagonists via Structure-Based Rational Design. Hu Z, Tanji H, Jiang S, Zhang S, Koo K, Chan J, Sakaniwa K, Ohto U, Candia A, Shimizu T, Yin H. Cell Chem Biol 25 1286-1291.e3 (2018)
  99. Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti. Saucereau Y, Wilson TH, Tang MCK, Moncrieffe MC, Hardwick SW, Chirgadze DY, Soares SG, Marcaida MJ, Gay NJ, Gangloff M. Nat Commun 13 5110 (2022)
  100. Structure-Based Optimization of a Fragment-like TLR8 Binding Screening Hit to an In Vivo Efficacious TLR7/8 Antagonist. Betschart C, Faller M, Zink F, Hemmig R, Blank J, Vangrevelinghe E, Bourrel M, Glatthar R, Behnke D, Barker K, Heizmann A, Angst D, Nimsgern P, Jacquier S, Junt T, Zipfel G, Ruzzante G, Loetscher P, Limonta S, Hawtin S, Andre CB, Boulay T, Feifel R, Knoepfel T. ACS Med Chem Lett 13 658-664 (2022)
  101. TIRAP/Mal Positively Regulates TLR8-Mediated Signaling via IRF5 in Human Cells. Nilsen KE, Skjesol A, Frengen Kojen J, Espevik T, Stenvik J, Yurchenko M. Biomedicines 10 1476 (2022)
  102. The Bacterial Product Violacein Exerts an Immunostimulatory Effect Via TLR8. Venegas FA, Köllisch G, Mark K, Diederich WE, Kaufmann A, Bauer S, Chavarría M, Araya JJ, García-Piñeres AJ. Sci Rep 9 13661 (2019)
  103. The Signal Peptide and Chaperone UNC93B1 Both Influence TLR8 Ectodomain Intracellular Endosomal Localization. Ao D, Liu X, Jiang S, Xu Y, Zheng W, Chen N, Meurens F, Zhu J. Vaccines (Basel) 10 14 (2021)
  104. The architecture of transmembrane and cytoplasmic juxtamembrane regions of Toll-like receptors. Kornilov FD, Shabalkina AV, Lin C, Volynsky PE, Kot EF, Kayushin AL, Lushpa VA, Goncharuk MV, Arseniev AS, Goncharuk SA, Wang X, Mineev KS. Nat Commun 14 1503 (2023)
  105. The emerging chemical patterns applied in predicting human toll-like receptor 8 agonists. Huang S, Mei H, Zhang D, Ren Y, Kevin M, Pan X. Medchemcomm 9 1961-1971 (2018)


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