- EMDB-30001: Cryo-EM reconstruction of TLR7/Cpd-7 (DSR-139970) complex in open form -
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基本情報
登録情報
データベース: EMDB / ID: EMD-30001
タイトル
Cryo-EM reconstruction of TLR7/Cpd-7 (DSR-139970) complex in open form
マップデータ
試料
複合体: TLR7/Cpd-7 (DSR-139970) complex
機能・相同性
機能・相同性情報
toll-like receptor 7 signaling pathway / response to cGMP / siRNA binding / early phagosome / positive regulation of macrophage cytokine production / pattern recognition receptor activity / toll-like receptor signaling pathway / positive regulation of interferon-alpha production / canonical NF-kappaB signal transduction / positive regulation of chemokine production ...toll-like receptor 7 signaling pathway / response to cGMP / siRNA binding / early phagosome / positive regulation of macrophage cytokine production / pattern recognition receptor activity / toll-like receptor signaling pathway / positive regulation of interferon-alpha production / canonical NF-kappaB signal transduction / positive regulation of chemokine production / JNK cascade / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / regulation of protein phosphorylation / cellular response to virus / cellular response to mechanical stimulus / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of interleukin-6 production / positive regulation of type II interferon production / double-stranded RNA binding / defense response to virus / single-stranded RNA binding / receptor complex / lysosome / endosome / inflammatory response / innate immune response / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / metal ion binding / plasma membrane 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2020 タイトル: Structural analysis reveals TLR7 dynamics underlying antagonism. 著者: Shingo Tojo / Zhikuan Zhang / Hiroyuki Matsui / Masahiro Tahara / Mitsunori Ikeguchi / Mami Kochi / Mami Kamada / Hideki Shigematsu / Akihisa Tsutsumi / Naruhiko Adachi / Takuma Shibata / ...著者: Shingo Tojo / Zhikuan Zhang / Hiroyuki Matsui / Masahiro Tahara / Mitsunori Ikeguchi / Mami Kochi / Mami Kamada / Hideki Shigematsu / Akihisa Tsutsumi / Naruhiko Adachi / Takuma Shibata / Masaki Yamamoto / Masahide Kikkawa / Toshiya Senda / Yoshiaki Isobe / Umeharu Ohto / Toshiyuki Shimizu / 要旨: 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 ...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.