4R07

Crystal structure of human TLR8 in complex with ORN06

Summary for 4R07

• Entry DOI: 10.2210/pdb4r07/pdb
• Related: 4R08 4R09 4R0A
• Descriptor: Toll-like receptor 8, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: leucine rich repeat, glycosylation, innate immunity, rna recognition, rna receptor, rna binding, antiviral binding, antitumor drug binding, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 386101.78

Authors

Tanji, H.,Ohto, U.,Shibata, T.,Taoka, M.,Yamauchi, Y.,Isobe, T.,Miyake, K.,Shimizu, T. (deposition date: 2014-07-30, release date: 2015-01-14, Last modification date: 2024-10-30)

Primary citation

Tanji, H.,Ohto, U.,Shibata, T.,Taoka, M.,Yamauchi, Y.,Isobe, T.,Miyake, K.,Shimizu, T.
Toll-like receptor 8 senses degradation products of single-stranded RNA
Nat.Struct.Mol.Biol., 22:109-115, 2015

PubMed 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.

PubMed: 25599397
DOI: 10.1038/nsmb.2943

Experimental method

X-RAY DIFFRACTION (2 Å)