4R09: Crystal Structure Of Human Tlr8 In Complex With Orn06s

Citation:
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.
PDB ID: 4R09Download
MMDB ID: 126057
PDB Deposition Date: 2014/7/30
Updated in MMDB: 2015/02
Experimental Method:
x-ray diffraction
Resolution: 2.62  Å
Source Organism:
Similar Structures:
Biological Unit for 4R09: dimeric; determined by author and by software (PISA)

Citing MMDB
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