+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7wv3 | |||||||||
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タイトル | Toll-like receptor3 linear cluster | |||||||||
要素 |
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キーワード | IMMUNE SYSTEM/RNA / Toll-like receptor / dsRNA / Innate immunity / Receptor / IMMUNE SYSTEM / IMMUNE SYSTEM-RNA complex | |||||||||
機能・相同性 | 機能・相同性情報 TLR3 deficiency - HSE / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / response to dsRNA / TRAF3 deficiency - HSE / regulation of dendritic cell cytokine production / Toll Like Receptor 3 (TLR3) Cascade / I-kappaB phosphorylation ...TLR3 deficiency - HSE / UNC93B1 deficiency - HSE / TICAM1 deficiency - HSE / type III interferon production / positive regulation of type III interferon production / response to dsRNA / TRAF3 deficiency - HSE / regulation of dendritic cell cytokine production / Toll Like Receptor 3 (TLR3) Cascade / I-kappaB phosphorylation / TLR3-mediated TICAM1-dependent programmed cell death / inflammatory response to wounding / activation of NF-kappaB-inducing kinase activity / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / detection of virus / RIP-mediated NFkB activation via ZBP1 / hyperosmotic response / endolysosome membrane / positive regulation of cytokine production involved in inflammatory response / Trafficking and processing of endosomal TLR / positive regulation of macrophage cytokine production / pattern recognition receptor activity / toll-like receptor signaling pathway / RSV-host interactions / cellular response to exogenous dsRNA / response to exogenous dsRNA / negative regulation of osteoclast differentiation / positive regulation of interferon-alpha production / cellular response to interferon-beta / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / JNK cascade / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / positive regulation of interleukin-12 production / positive regulation of interferon-beta production / extracellular matrix / TICAM1, RIP1-mediated IKK complex recruitment / 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 / transmembrane signaling receptor activity / cellular response to virus / cellular response to type II interferon / positive regulation of inflammatory response / positive regulation of interleukin-6 production / cellular response to xenobiotic stimulus / positive regulation of type II interferon production / positive regulation of angiogenesis / male gonad development / positive regulation of tumor necrosis factor production / double-stranded RNA binding / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / endosome membrane / early endosome / defense response to bacterium / positive regulation of apoptotic process / Golgi membrane / lysosomal membrane / innate immune response / endoplasmic reticulum membrane / positive regulation of gene expression / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / identical protein binding / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) synthetic construct (人工物) | |||||||||
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: 2.26 Å | |||||||||
データ登録者 | Lim, C.S. / Jang, Y.H. / Lee, G.Y. / Han, G.M. / Lee, J.O. | |||||||||
資金援助 | 韓国, 2件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand. 著者: Chan Seok Lim / Yoon Ha Jang / Ga Young Lee / Gu Min Han / Hye Jin Jeong / Ji Won Kim / Jie-Oh Lee / 要旨: Toll-like Receptor 3 (TLR3) initiates a potent anti-viral immune response by binding to double-stranded RNA ligands. Previous crystallographic studies showed that TLR3 forms a homodimer when bound to ...Toll-like Receptor 3 (TLR3) initiates a potent anti-viral immune response by binding to double-stranded RNA ligands. Previous crystallographic studies showed that TLR3 forms a homodimer when bound to a 46-base pair RNA ligand. However, this short RNA fails to initiate a robust immune response. To obtain structural insights into the length dependency of TLR3 ligands, we determine the cryo-electron microscopy structure of full-length TLR3 in a complex with a synthetic RNA ligand with an average length of ~400 base pairs. In the structure, the dimeric TLR3 units are clustered along the double-stranded RNA helix in a highly organized and cooperative fashion with a uniform inter-dimer spacing of 103 angstroms. The intracellular and transmembrane domains are dispensable for the clustering because their deletion does not interfere with the cluster formation. Our structural observation suggests that ligand-induced clustering of TLR3 dimers triggers the ordered assembly of intracellular signaling adaptors and initiates a robust innate immune response. | |||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7wv3.cif.gz | 567.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7wv3.ent.gz | 453.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7wv3.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7wv3_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7wv3_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 7wv3_validation.xml.gz | 73.2 KB | 表示 | |
CIF形式データ | 7wv3_validation.cif.gz | 114.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/wv/7wv3 ftp://data.pdbj.org/pub/pdb/validation_reports/wv/7wv3 | HTTPS FTP |
-関連構造データ
関連構造データ | 32844MC 7wv4C 7wv5C 7wveC 7wvfC 7wvjC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 102376.281 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TLR3 / 細胞株 (発現宿主): HEK293s GnTi- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O15455 #2: RNA鎖 | | 分子量: 24369.598 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) #3: RNA鎖 | | 分子量: 26370.277 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) #4: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #5: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | N | |
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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 |
-試料調製
構成要素 |
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分子量 | 実験値: NO | ||||||||||||||||||||||||
由来(天然) | 生物種: Human (ヒト) | ||||||||||||||||||||||||
由来(組換発現) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||||||
緩衝液 | pH: 5.5 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 7.2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
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: 277 K |
-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 |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2100 nm / 最小 デフォーカス(公称値): 700 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 2.26 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 982514 / 対称性のタイプ: POINT |
原子モデル構築 | プロトコル: RIGID BODY FIT |
原子モデル構築 | PDB-ID: 3ULU |