4R08

Crystal structure of human TLR8 in complex with ssRNA40

4R08 の概要

• エントリーDOI: 10.2210/pdb4r08/pdb
• 関連するPDBエントリー: 4R07 4R09 4R0A
• 分子名称: Toll-like receptor 8, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: leucine rich repeat, glycosylation, innate immunity, rna recognition, rna receptor, rna binding, antiviral binding, antitumor drug binding, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 385615.36

構造登録者

Tanji, H.,Ohto, U.,Shimizu, T. (登録日: 2014-07-30, 公開日: 2015-01-14, 最終更新日: 2020-07-29)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)