5GMH

Crystal structure of monkey TLR7 in complex with R848

5GMH の概要

• エントリーDOI: 10.2210/pdb5gmh/pdb
• 関連するPDBエントリー: 5GMF 5GMG
• 分子名称: Toll-like receptor 7, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 1-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol, ... (6 entities in total)
• 機能のキーワード: immune system, tlr7, innate immunity, ssrna recogniton
• 由来する生物種: Macaca mulatta (Rhesus macaque)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 195275.54

構造登録者

Zhang, Z.,Ohto, U.,Shimizu, T. (登録日: 2016-07-14, 公開日: 2016-11-02, 最終更新日: 2023-11-08)

主引用文献

Zhang, Z.,Ohto, U.,Shibata, T.,Krayukhina, E.,Taoka, M.,Yamauchi, Y.,Tanji, H.,Isobe, T.,Uchiyama, S.,Miyake, K.,Shimizu, T.
Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor for Guanosine and Single-Stranded RNA
Immunity, 45:737-748, 2016

PubMed Abstract: Toll-like receptor 7 (TLR7) is a single-stranded RNA (ssRNA) sensor in innate immunity and also responds to guanosine and chemical ligands, such as imidazoquinoline compounds. However, TLR7 activation mechanism by these ligands remain largely unknown. Here, we generated crystal structures of three TLR7 complexes, and found that all formed an activated m-shaped dimer with two ligand-binding sites. The first site conserved in TLR7 and TLR8 was used for small ligand-binding essential for its activation. The second site spatially distinct from that of TLR8 was used for a ssRNA-binding that enhanced the affinity of the first-site ligands. The first site preferentially recognized guanosine and the second site specifically bound to uridine moieties in ssRNA. Our structural, biochemical, and mutagenesis studies indicated that TLR7 is a dual receptor for guanosine and uridine-containing ssRNA. Our findings have important implications for understanding of TLR7 function, as well as for therapeutic manipulation of TLR7 activation.

PubMed: 27742543
DOI: 10.1016/j.immuni.2016.09.011

実験手法

X-RAY DIFFRACTION (2.2 Å)