+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7wvf | |||||||||
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タイトル | ectoTLR3-mAb12-poly(I:C) complex | |||||||||
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 / toll-like receptor 3 signaling pathway / necroptotic signaling pathway / detection of virus / activation of NF-kappaB-inducing kinase activity / 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 / cellular response to interferon-beta / positive regulation of interferon-alpha production / extrinsic apoptotic signaling pathway / positive regulation of chemokine production / JNK cascade / 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 / TICAM1, RIP1-mediated IKK complex recruitment / extracellular matrix / positive regulation of interleukin-8 production / positive regulation of JNK cascade / microglial cell activation / cellular response to virus / cellular response to type II interferon / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to mechanical stimulus / transmembrane signaling receptor activity / positive regulation of angiogenesis / male gonad development / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / double-stranded RNA binding / positive regulation of type II interferon production / cellular response to xenobiotic stimulus / signaling receptor activity / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / early endosome / endosome membrane / defense response to bacterium / positive regulation of apoptotic process / Golgi membrane / lysosomal membrane / innate immune response / positive regulation of gene expression / endoplasmic reticulum membrane / 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: 3.91 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 | 7wvf.cif.gz | 314.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7wvf.ent.gz | 253 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7wvf.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 | 7wvf_validation.pdf.gz | 796.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7wvf_full_validation.pdf.gz | 809.8 KB | 表示 | |
XML形式データ | 7wvf_validation.xml.gz | 47.2 KB | 表示 | |
CIF形式データ | 7wvf_validation.cif.gz | 72.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/wv/7wvf ftp://data.pdbj.org/pub/pdb/validation_reports/wv/7wvf | HTTPS FTP |
-関連構造データ
関連構造データ | 32852MC 7wv3C 7wv4C 7wv5C 7wveC 7wvjC C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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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: 78423.375 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TLR3 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: O15455 #2: RNA鎖 | | 分子量: 13993.408 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: 15143.821 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) #4: 抗体 | | 分子量: 27712.111 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Trichoplusia ni (イラクサキンウワバ) |
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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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由来(天然) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||||||
由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) | ||||||||||||||||||||||||
緩衝液 | pH: 5.5 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 1 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
顕微鏡 | モデル: TFS GLACIOS |
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電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 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): 2500 nm / 最小 デフォーカス(公称値): 900 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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対称性 | 点対称性: C1 (非対称) |
3次元再構成 | 解像度: 3.91 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 136835 / 対称性のタイプ: POINT |