- PDB-7das: Mouse Toll-like receptor 3 ectodomain in complex with lncRNA Rmrp... -
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基本情報
登録情報
データベース: PDB / ID: 7das
タイトル
Mouse Toll-like receptor 3 ectodomain in complex with lncRNA Rmrp in lapped form
要素
RNA component of mitochondrial RNAase P (Rmrp), RNase MRP RNA
Toll-like receptor 3
キーワード
RNA BINDING PROTEIN/RNA / complex / innate immune system / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex
機能・相同性
機能・相同性情報
type III interferon production / positive regulation of type III interferon production / regulation of dendritic cell cytokine production / inflammatory response to wounding / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / positive regulation of cytokine production involved in inflammatory response / positive regulation of macrophage cytokine production / toll-like receptor signaling pathway / pattern recognition receptor activity ...type III interferon production / positive regulation of type III interferon production / regulation of dendritic cell cytokine production / inflammatory response to wounding / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / positive regulation of cytokine production involved in inflammatory response / positive regulation of macrophage cytokine production / toll-like receptor signaling pathway / pattern recognition receptor activity / cellular response to exogenous dsRNA / response to exogenous dsRNA / ubiquitin-like protein ligase binding / positive regulation of interferon-alpha production / positive regulation of type I interferon production / cellular response to interferon-beta / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / JNK cascade / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / positive regulation of interleukin-8 production / positive regulation of JNK cascade / microglial cell activation / cellular response to mechanical stimulus / positive regulation of non-canonical NF-kappaB signal transduction / defense response / cellular response to virus / cellular response to type II interferon / positive regulation of interleukin-6 production / response to virus / male gonad development / cellular response to xenobiotic stimulus / positive regulation of type II interferon production / positive regulation of angiogenesis / positive regulation of tumor necrosis factor production / transmembrane signaling receptor activity / MAPK cascade / double-stranded RNA binding / defense response to virus / early endosome / positive regulation of canonical NF-kappaB signal transduction / endosome membrane / positive regulation of apoptotic process / innate immune response / endoplasmic reticulum membrane / cell surface / positive regulation of transcription by RNA polymerase II / identical protein binding / plasma membrane 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
81788101
中国
引用
ジャーナル: Cell Res / 年: 2025 タイトル: Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation. 著者: Shikun Zhang / Bo Li / Lun Liu / Dongsheng Gong / Deyu Zhang / Fengjiang Liu / Xiuna Yang / Hua Qin / Deling Kong / Shuyang Zhang / Zihe Rao / Xuetao Cao / 要旨: The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation ...The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3. Furthermore, K42 residue of TLR3 is essential for binding to Rmrp and subsequent dimerization. Rmrp dissociates from TLR3 following endosomal acidification, generating a matured TLR3 dimer which is primed for innate recognition and activation. Myeloid-cell deficiency of Rmrp reduces TLR3 dimerization and attenuates TLR3-mediated antiviral responses against influenza A both in vitro and in vivo. These findings elucidate the structural mode of self RNA Rmrp-primed TLR3 dimerization and ready for efficient innate recognition on endosomal membrane, extending our knowledge of how membrane-associated TLRs pre-dimerize and suggesting a new function of subcellular localized self RNAs in empowering innate activation.