Cited by 404Immune Response and InflammationInflammasome and immune disordersinterferon and immune responses

Toll-like receptor 8 senses degradation products of single-stranded RNA

Tanji, Hiromi, Ohto, Umeharu, Shibata, Takuma, Taoka, Masato, Yamauchi, Yoshio, Isobe, Toshiaki, Miyake, Kensuke, Shimizu, Toshiyuki·2015·Nature Structural & Molecular Biology

Abstract

Toll-like receptor 8 (TLR8) recognizes viral or bacterial single-stranded RNA (ssRNA) and activates innate immune systems. TLR8 is activated by uridine- and guanosine-rich ssRNA as well as by certain synthetic chemicals; however, the molecular basis for ssRNA recognition has remained unknown. In this study, to elucidate the recognition mechanism of ssRNA, we determined the crystal structures of human TLR8 in complex with ssRNA. TLR8 recognized two degradation products of ssRNA—uridine and a short oligonucleotide—at two distinct sites: uridine bound the site on the dimerization interface where small chemical ligands are recognized, whereas short oligonucleotides bound a newly identified site on the concave surface of the TLR8 horseshoe structure. Site-directed mutagenesis revealed that both binding sites were essential for activation of TLR8 by ssRNA. These results demonstrate that TLR8 is a sensor for both uridine and a short oligonucleotide derived from RNA.

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Crossref · 10.1038/nsmb.2943

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  • The ligands of TLR7 and TLR8 are degradation products of RNA including short stretches of ssRNA and nucleosides.

    “Recently, the ligands of TLR7 and TLR8 have been reported as degradation products of RNA including short stretches of ssRNA and nucleosides (Tanji et al. 2015; Zhang et al. 2016).”

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Authors
Tanji, H., Ohto, U., Shibata, T., Taoka, M., Yamauchi, Y., Isobe, T., Miyake, K., & Shimizu, T.
Affiliations
  • The University of Tokyo (JP)
  • Japan Science and Technology Agency (JP)
  • Tokyo Metropolitan University (JP)
  • Institute of Medical Science, The University of Tokyo (JP)
Corresponding author
Shimizu, Toshiyuki
Venue
Nature Structural & Molecular Biology
Published
2015-01-19
Volume
22
Issue
2
Pages
109-115
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2147763501
Cited by
404
References
41
Citations by year
2026: 29 · 2025: 34 · 2024: 41 · 2023: 40 · 2022: 38 · 2021: 62 · 2020: 31 · 2019: 30 · 2018: 28 · 2017: 26 · 2016: 30 · 2015: 15
FWCI
16.27
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (26670235, 15J12485, 25253032, 25291010)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
TLR8, single-stranded RNA, uridine, innate immunity, ligand recognition
MeSH terms
Animals, Binding Sites, Calorimetry, Cell Line, Chromatography, Liquid, Drosophila, Humans, RNA, Mass Spectrometry, Mutagenesis, Site-Directed, Protein Structure, Tertiary, Crystallography, X-Ray, Toll-Like Receptor 8

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