positive regulation of IP-10 production / regulation of peroxisome organization / RIG-I binding / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of myeloid dendritic cell cytokine production / CARD domain binding / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / protein localization to mitochondrion / positive regulation of response to cytokine stimulus / positive regulation of type I interferon-mediated signaling pathway ...positive regulation of IP-10 production / regulation of peroxisome organization / RIG-I binding / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of myeloid dendritic cell cytokine production / CARD domain binding / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / protein localization to mitochondrion / positive regulation of response to cytokine stimulus / positive regulation of type I interferon-mediated signaling pathway / peroxisomal membrane / TRAF6 mediated IRF7 activation / negative regulation of type I interferon-mediated signaling pathway / positive regulation of NLRP3 inflammasome complex assembly / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of viral genome replication / type I interferon-mediated signaling pathway / cellular response to exogenous dsRNA / TRAF6 mediated NF-kB activation / antiviral innate immune response / positive regulation of type I interferon production / positive regulation of interferon-alpha production / signaling adaptor activity / ubiquitin ligase complex / positive regulation of defense response to virus by host / activation of innate immune response / positive regulation of interferon-beta production / molecular condensate scaffold activity / positive regulation of interleukin-8 production / Negative regulators of DDX58/IFIH1 signaling / mitochondrial membrane / DDX58/IFIH1-mediated induction of interferon-alpha/beta / PKR-mediated signaling / Evasion by RSV of host interferon responses / positive regulation of DNA-binding transcription factor activity / positive regulation of protein import into nucleus / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / Ovarian tumor domain proteases / TRAF3-dependent IRF activation pathway / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / mitochondrial outer membrane / molecular adaptor activity / defense response to bacterium / positive regulation of protein phosphorylation / innate immune response / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / identical protein binding 類似検索 - 分子機能
ジャーナル: Mol Cell / 年: 2014 タイトル: Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I. 著者: Bin Wu / Alys Peisley / David Tetrault / Zongli Li / Edward H Egelman / Katharine E Magor / Thomas Walz / Pawel A Penczek / Sun Hur / 要旨: RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD(MAVS)), and requires ...RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD(MAVS)), and requires its interaction with the tandem CARDs of RIG-I (2CARD(RIG-I)). However, the precise nature of the interaction between 2CARD(RIG-I) and CARD(MAVS), and how this interaction leads to CARD(MAVS) filament assembly, has been unclear. Here we report a 3.6 Å electron microscopy structure of the CARD(MAVS) filament and a 3.4 Å crystal structure of the 2CARD(RIG-I):CARD(MAVS) complex, representing 2CARD(RIG-I) "caught in the act" of nucleating the CARD(MAVS) filament. These structures, together with functional analyses, show that 2CARD(RIG-I) acts as a template for the CARD(MAVS) filament assembly, by forming a helical tetrameric structure and recruiting CARD(MAVS) along its helical trajectory. Our work thus reveals that signal activation by RIG-I occurs by imprinting its helical assembly architecture on MAVS, a previously uncharacterized mechanism of signal transmission.
A: Mitochondrial antiviral-signaling protein B: Mitochondrial antiviral-signaling protein C: Mitochondrial antiviral-signaling protein D: Mitochondrial antiviral-signaling protein E: Mitochondrial antiviral-signaling protein G: Mitochondrial antiviral-signaling protein I: Mitochondrial antiviral-signaling protein L: Mitochondrial antiviral-signaling protein
装置: FEI VITROBOT MARK I / 凍結剤: NITROGEN / 詳細: Plunged in liquid nitrogen (FEI VITROBOT MARK I)
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電子顕微鏡撮影
実験機器
モデル: Tecnai F20 / 画像提供: FEI Company
顕微鏡
モデル: FEI TECNAI F20 / 日付: 2013年8月10日 詳細: Movies were recorded at liquid nitrogen temperature with a K2 Summit direct detector device camera operated in super-resolution mode with dose-fractionation.
電子線照射量: 31 e/Å2 / フィルム・検出器のモデル: GATAN K2 (4k x 4k)
電子光学装置
エネルギーフィルター名称: FEI
画像スキャン
デジタル画像の数: 1863
放射
プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray
放射波長
相対比: 1
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解析
EMソフトウェア
ID
名称
カテゴリ
1
PHENIX
モデルフィッティング
2
Helicon
3次元再構成
らせん対称
回転角度/サブユニット: 101.1 ° / 軸方向距離/サブユニット: 5.13 Å / らせん対称軸の対称性: C1
3次元再構成
解像度: 3.64 Å / 解像度の算出法: FSC 0.5 CUT-OFF / ピクセルサイズ(公称値): 1.1 Å / ピクセルサイズ(実測値): 1.1 Å 詳細: The electron density map of the filament was reconstructed using a helical geometrically constrained reconstruction approach (Helicon). 対称性のタイプ: HELICAL
原子モデル構築
B value: 136.08 / プロトコル: RIGID BODY FIT / 空間: RECIPROCAL / Target criteria: Cross-correlation coefficient 詳細: METHOD--local refinement REFINEMENT PROTOCOL--rigid body with TLS
精密化
解像度: 3.64→99.2 Å / SU ML: 0.87 / σ(F): 1 / 位相誤差: 37.36 / 立体化学のターゲット値: ML
Rfactor
反射数
%反射
Rfree
0.2764
1729
5.1 %
Rwork
0.2377
32187
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obs
0.2397
33916
99.94 %
溶媒の処理
減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å / 溶媒モデル: FLAT BULK SOLVENT MODEL