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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 6ggs | ||||||
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タイトル | Structure of RIP2 CARD filament | ||||||
![]() | Receptor-interacting serine/threonine-protein kinase 2 | ||||||
![]() | TRANSFERASE / CARD / RIP2 / filament / helical | ||||||
機能・相同性 | ![]() response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / positive regulation of xenophagy / LIM domain binding / xenophagy / CD4-positive, alpha-beta T cell proliferation ...response to interleukin-18 / positive regulation of T-helper 1 cell differentiation / toll-like receptor 2 signaling pathway / positive regulation of cytokine-mediated signaling pathway / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / positive regulation of xenophagy / LIM domain binding / xenophagy / CD4-positive, alpha-beta T cell proliferation / nucleotide-binding oligomerization domain containing 1 signaling pathway / positive regulation of protein K63-linked ubiquitination / positive regulation of stress-activated MAPK cascade / cellular response to muramyl dipeptide / CARD domain binding / positive regulation of immature T cell proliferation in thymus / caspase binding / JUN kinase kinase kinase activity / cellular response to peptidoglycan / response to interleukin-12 / positive regulation of CD4-positive, alpha-beta T cell proliferation / activation of cysteine-type endopeptidase activity / nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of macrophage cytokine production / toll-like receptor 4 signaling pathway / response to exogenous dsRNA / cellular response to lipoteichoic acid / canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / signaling adaptor activity / positive regulation of chemokine production / stress-activated MAPK cascade / JNK cascade / lipopolysaccharide-mediated signaling pathway / p75NTR recruits signalling complexes / positive regulation of interleukin-12 production / ERK1 and ERK2 cascade / positive regulation of interleukin-2 production / positive regulation of interferon-beta production / response to interleukin-1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / positive regulation of protein ubiquitination / activated TAK1 mediates p38 MAPK activation / positive regulation of JNK cascade / non-specific protein-tyrosine kinase / TAK1-dependent IKK and NF-kappa-B activation / non-membrane spanning protein tyrosine kinase activity / NOD1/2 Signaling Pathway / protein homooligomerization / cytokine-mediated signaling pathway / Interleukin-1 signaling / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of type II interferon production / Ovarian tumor domain proteases / Downstream TCR signaling / positive regulation of protein binding / positive regulation of peptidyl-serine phosphorylation / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / positive regulation of canonical NF-kappaB signal transduction / adaptive immune response / vesicle / positive regulation of ERK1 and ERK2 cascade / cytoskeleton / non-specific serine/threonine protein kinase / defense response to Gram-positive bacterium / defense response to bacterium / inflammatory response / positive regulation of apoptotic process / phosphorylation / innate immune response / protein serine kinase activity / signaling receptor binding / protein serine/threonine kinase activity / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / endoplasmic reticulum / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / ATP binding / identical protein binding / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.94 Å | ||||||
![]() | Pellegrini, E. / Cusack, S. / Desfosses, A. / Schoehn, G. / Malet, H. / Gutsche, I. / Sachse, C. / Hons, M. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: RIP2 filament formation is required for NOD2 dependent NF-κB signalling. 著者: Erika Pellegrini / Ambroise Desfosses / Arndt Wallmann / Wiebke Manuela Schulze / Kristina Rehbein / Philippe Mas / Luca Signor / Stephanie Gaudon / Grasilda Zenkeviciute / Michael Hons / ...著者: Erika Pellegrini / Ambroise Desfosses / Arndt Wallmann / Wiebke Manuela Schulze / Kristina Rehbein / Philippe Mas / Luca Signor / Stephanie Gaudon / Grasilda Zenkeviciute / Michael Hons / Helene Malet / Irina Gutsche / Carsten Sachse / Guy Schoehn / Hartmut Oschkinat / Stephen Cusack / ![]() ![]() ![]() 要旨: Activation of the innate immune pattern recognition receptor NOD2 by the bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the downstream adaptor kinase RIP2, eventually ...Activation of the innate immune pattern recognition receptor NOD2 by the bacterial muramyl-dipeptide peptidoglycan fragment triggers recruitment of the downstream adaptor kinase RIP2, eventually leading to NF-κB activation and proinflammatory cytokine production. Here we show that full-length RIP2 can form long filaments mediated by its caspase recruitment domain (CARD), in common with other innate immune adaptor proteins. We further show that the NOD2 tandem CARDs bind to one end of the RIP2 CARD filament, suggesting a mechanism for polar filament nucleation by activated NOD2. We combine X-ray crystallography, solid-state NMR and high-resolution cryo-electron microscopy to determine the atomic structure of the helical RIP2 CARD filament, which reveals the intermolecular interactions that stabilize the assembly. Using structure-guided mutagenesis, we demonstrate the importance of RIP2 polymerization for the activation of NF-κB signalling by NOD2. Our results could be of use to develop new pharmacological strategies to treat inflammatory diseases characterised by aberrant NOD2 signalling. | ||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 155.2 KB | 表示 | ![]() |
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PDB形式 | ![]() | 125.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 861.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 877.4 KB | 表示 | |
XML形式データ | ![]() | 23.8 KB | 表示 | |
CIF形式データ | ![]() | 37.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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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: 12586.478 Da / 分子数: 10 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 発現宿主: ![]() ![]() 参照: UniProt: O43353, non-specific serine/threonine protein kinase, non-specific protein-tyrosine kinase |
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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: HELICAL ARRAY / 3次元再構成法: らせん対称体再構成法 |
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試料調製
構成要素 | 名称: Helical assemble of the CARD domain of RIP2 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Tecnai Polara / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI POLARA 300 |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 1.25 e/Å2 フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
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解析
EMソフトウェア | 名称: SPRING / カテゴリ: 3次元再構成 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
らせん対称 | 回転角度/サブユニット: -101.12 ° / 軸方向距離/サブユニット: 4.848 Å / らせん対称軸の対称性: C1 |
3次元再構成 | 解像度: 3.94 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 9661 / 対称性のタイプ: HELICAL |