5ZSD

Crystal structure of monkey TLR7 in complex with IMDQ and GGUUGG

5ZSD の概要

• エントリーDOI: 10.2210/pdb5zsd/pdb
• 分子名称: Toll-like receptor 7, RNA (5'-R(P*UP*UP*GP*A)-3'), 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: innate immunity toll-like receptors, immune system
• 由来する生物種: Macaca mulatta (Rhesus macaque); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 199550.29

構造登録者

Zhang, Z.,Ohto, U.,Shimizu, T. (登録日: 2018-04-28, 公開日: 2019-01-30, 最終更新日: 2024-11-13)

主引用文献

Zhang, Z.,Ohto, U.,Shibata, T.,Taoka, M.,Yamauchi, Y.,Sato, R.,Shukla, N.M.,David, S.A.,Isobe, T.,Miyake, K.,Shimizu, T.
Structural Analyses of Toll-like Receptor 7 Reveal Detailed RNA Sequence Specificity and Recognition Mechanism of Agonistic Ligands.
Cell Rep, 25:3371-3381.e5, 2018

PubMed Abstract: Toll-like receptor 7 (TLR7) is an innate immune receptor for single-stranded RNA (ssRNA) and has important roles in infectious diseases. We previously reported that TLR7 shows synergistic activation in response to two ligands, guanosine and ssRNA. However, the specific ssRNA sequence preference, detailed recognition mode of TLR7 and its ligand, and molecular determinants of TLR7 and TLR8 selectivity remain unknown. Here, we report on TLR7 from a large-scale crystallographic study combined with a multifaceted approach. We reveal that successive uridine-containing ssRNAs fully or moderately bind TLR7, whereas single uridine-containing ssRNAs have reduced affinities. We also reveal the detailed relationships between the chemical structures of ligands and their binding to TLR7. We demonstrate that an engineered TLR8 mutant alters its responsiveness to TLR7-specific ligands. Finally, we identify guanosine 2',3'-cyclic phosphate (2',3'-cGMP) as a possible endogenous ligand for TLR7 with greater affinity than guanosine. The abundant structural information will facilitate future development of treatments targeting TLR7.

PubMed: 30566863
DOI: 10.1016/j.celrep.2018.11.081

実験手法

X-RAY DIFFRACTION (2.603 Å)