6LW0

Crystal structure of TLR7/Cpd-6 (DSR-139293) complex

6LW0 の概要

• エントリーDOI: 10.2210/pdb6lw0/pdb
• 分子名称: Toll-like receptor 7, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: tlr7, antagonist, immune system
• 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: 194903.15

構造登録者

Zhang, Z.,Ohto, U.,Shimizu, T. (登録日: 2020-02-06, 公開日: 2020-11-11, 最終更新日: 2024-10-30)

主引用文献

Tojo, S.,Zhang, Z.,Matsui, H.,Tahara, M.,Ikeguchi, M.,Kochi, M.,Kamada, M.,Shigematsu, H.,Tsutsumi, A.,Adachi, N.,Shibata, T.,Yamamoto, M.,Kikkawa, M.,Senda, T.,Isobe, Y.,Ohto, U.,Shimizu, T.
Structural analysis reveals TLR7 dynamics underlying antagonism.
Nat Commun, 11:5204-5204, 2020

PubMed Abstract: Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs and nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent TLR7 agonists, we develop a series of TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography and cryo-electron microscopy, we identify the open conformation of the receptor and reveal the structural equilibrium between open and closed conformations that underlies TLR7 antagonism, as well as the detailed mechanism by which TLR7-specific antagonists bind to their binding pocket in TLR7. Our work provides small-molecule TLR7-specific antagonists and suggests the TLR7-targeting strategy for treating autoimmune diseases.

PubMed: 33060576
DOI: 10.1038/s41467-020-19025-z

実験手法

X-RAY DIFFRACTION (2.6 Å)