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PDBsum entry 4r09
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Immune system
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PDB id
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4r09
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References listed in PDB file
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Key reference
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Title
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Toll-Like receptor 8 senses degradation products of single-Stranded RNA.
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Authors
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H.Tanji,
U.Ohto,
T.Shibata,
M.Taoka,
Y.Yamauchi,
T.Isobe,
K.Miyake,
T.Shimizu.
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Ref.
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Nat Struct Biol, 2015,
22,
109-115.
[DOI no: ]
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PubMed id
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Abstract
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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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