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基本情報
登録情報 | データベース: PDB / ID: 7da7 | ||||||
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タイトル | Mouse Toll-like receptor 3 ectodomain in complex with lncRNA Rmrp in elongated form | ||||||
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![]() | RNA BINDING PROTEIN/RNA / complex / innate immune system / RNA BINDING PROTEIN / RNA BINDING PROTEIN-RNA complex | ||||||
機能・相同性 | ![]() 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 / JNK cascade / extrinsic apoptotic signaling pathway / 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 / endosome membrane / positive regulation of canonical NF-kappaB signal transduction / 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 | ||||||
生物種 | ![]() ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.47 Å | ||||||
![]() | Li, B. / Cao, X. | ||||||
資金援助 | ![]()
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![]() | ![]() 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. | ||||||
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 274.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 212.8 KB | 表示 | ![]() |
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文書・要旨 | ![]() | 848 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 874.9 KB | 表示 | |
XML形式データ | ![]() | 43.2 KB | 表示 | |
CIF形式データ | ![]() | 67.4 KB | 表示 | |
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-関連構造データ
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 78101.648 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: RNA鎖 | | 分子量: 48124.520 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() ![]() Has protein modification | Y | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Cryo-EM structure of mouse Toll-like receptor 3 ectodomain with C-domain of lncRNA Rmrp タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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分子量 | 値: 0.23 MDa / 実験値: YES |
由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 6 |
試料 | 濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: This sample was mono disperse. |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 281 K |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS / 詳細: Preliminary grid screening was preformed manually. |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 165000 X / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm / Calibrated defocus min: 1000 nm / 最大 デフォーカス(補正後): 2000 nm / Cs: 2.7 mm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER 最高温度: 78.5 K / 最低温度: 78.5 K |
撮影 | 平均露光時間: 5 sec. / 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 撮影したグリッド数: 2 / 実像数: 10617 |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 40 eV |
画像スキャン | 動画フレーム数/画像: 40 |
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解析
EMソフトウェア |
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画像処理 | 詳細: The selected images were normalized. | ||||||||||||||||||||||||||||||||||||
CTF補正 | 詳細: CTF correction was done by patch CTF correction. / タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 2545278 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.47 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 108128 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 97.5 / プロトコル: RIGID BODY FIT / Target criteria: correlation coefficient | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 3CIG PDB chain-ID: A / Accession code: 3CIG / Pdb chain residue range: 27-697 / Source name: PDB / タイプ: experimental model |