+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-6842 | |||||||||
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タイトル | Structure of RIP2 CARD domain | |||||||||
マップデータ | 200 A long segment of RIP-CARD filament | |||||||||
試料 |
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キーワード | Innate Immune signaling complex / IMMUNE SYSTEM (免疫系) / TRANSFERASE (転移酵素) | |||||||||
機能・相同性 | 機能・相同性情報 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 / LIM domain binding / positive regulation of xenophagy / CD4-positive, alpha-beta T cell proliferation / xenophagy ...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 / LIM domain binding / positive regulation of xenophagy / CD4-positive, alpha-beta T cell proliferation / xenophagy / nucleotide-binding oligomerization domain containing 1 signaling pathway / positive regulation of protein K63-linked ubiquitination / cellular response to muramyl dipeptide / caspase binding / positive regulation of immature T cell proliferation in thymus / CARD domain binding / JUN kinase kinase kinase activity / positive regulation of CD4-positive, alpha-beta T cell proliferation / cellular response to peptidoglycan / response to interleukin-12 / 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 / positive regulation of interferon-alpha production / cellular response to lipoteichoic acid / signaling adaptor activity / canonical NF-kappaB signal transduction / positive regulation of chemokine production / JNK cascade / lipopolysaccharide-mediated signaling pathway / ERK1 and ERK2 cascade / p75NTR recruits signalling complexes / positive regulation of interleukin-2 production / positive regulation of interferon-beta production / positive regulation of interleukin-12 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 protein ubiquitination / positive regulation of interleukin-1 beta production / activated TAK1 mediates p38 MAPK activation / positive regulation of JNK cascade / non-specific protein-tyrosine kinase / TAK1-dependent IKK and NF-kappa-B activation / NOD1/2 Signaling Pathway / non-membrane spanning protein tyrosine kinase activity / protein homooligomerization / positive regulation of interleukin-6 production / Interleukin-1 signaling / cytokine-mediated signaling pathway / positive regulation of peptidyl-tyrosine phosphorylation / Ovarian tumor domain proteases / positive regulation of type II interferon production / positive regulation of tumor necrosis factor production / Downstream TCR signaling / positive regulation of peptidyl-serine phosphorylation / positive regulation of NF-kappaB transcription factor activity / positive regulation of protein binding / T cell receptor signaling pathway / positive regulation of canonical NF-kappaB signal transduction / vesicle / 獲得免疫系 / positive regulation of ERK1 and ERK2 cascade / 細胞骨格 / non-specific serine/threonine protein kinase / defense response to Gram-positive bacterium / defense response to bacterium / 炎症 / positive regulation of apoptotic process / リン酸化 / signaling receptor binding / 自然免疫系 / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / 小胞体 / シグナル伝達 / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / ATP binding / identical protein binding / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 4.1 Å | |||||||||
データ登録者 | Wu B / Gong Q | |||||||||
資金援助 | シンガポール, 1件
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引用 | ジャーナル: Nat Commun / 年: 2018 タイトル: Structural basis of RIP2 activation and signaling. 著者: Qin Gong / Ziqi Long / Franklin L Zhong / Daniel Eng Thiam Teo / Yibo Jin / Zhan Yin / Zhao Zhi Boo / Yaming Zhang / Jiawen Zhang / Renliang Yang / Shashi Bhushan / Bruno Reversade / Zongli Li / Bin Wu / 要旨: Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting- ...Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an adapter protein that is critical for signal propagation of the Nucleotide-binding-oligomerization-domain-containing proteins 1/2 (NOD1 and NOD2). Dysregulation of this signaling pathway leads to defects in bacterial detection and in some cases autoimmune diseases. Here, we show that the Caspase-activation-and-recruitment-domain (CARD) of RIP2 (RIP2-CARD) forms oligomeric structures upon stimulation by either NOD1-CARD or NOD2-2CARD. We reconstitute this complex, termed the RIPosome in vitro and solve the cryo-EM filament structure of the active RIP2-CARD complex at 4.1 Å resolution. The structure suggests potential mechanisms by which CARD domains from NOD1 and NOD2 initiate the oligomerization process of RIP2-CARD. Together with structure guided mutagenesis experiments at the CARD-CARD interfaces, we demonstrate molecular mechanisms how RIP2 is activated and self-propagating such signal. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_6842.map.gz | 28.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-6842-v30.xml emd-6842.xml | 18 KB 18 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_6842_fsc.xml | 8.3 KB | 表示 | FSCデータファイル |
画像 | emd_6842.png | 87.3 KB | ||
Filedesc metadata | emd-6842.cif.gz | 5.7 KB | ||
その他 | emd_6842_additional.map.gz emd_6842_half_map_1.map.gz emd_6842_half_map_2.map.gz | 430.1 KB 23.4 MB 23.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-6842 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6842 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_6842.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | 200 A long segment of RIP-CARD filament | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.23 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: Cropped out central segment of 60 A, where...
ファイル | emd_6842_additional.map | ||||||||||||
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注釈 | Cropped out central segment of 60 A, where 12 RIP2-CARD were built into. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: unfiltered half 2 of 200 A RIP2-CARD filament
ファイル | emd_6842_half_map_1.map | ||||||||||||
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注釈 | unfiltered half 2 of 200 A RIP2-CARD filament | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: unfiltered half 1 of 200 A RIP2-CARD filament
ファイル | emd_6842_half_map_2.map | ||||||||||||
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注釈 | unfiltered half 1 of 200 A RIP2-CARD filament | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Active RIP2 signaling complex
全体 | 名称: Active RIP2 signaling complex |
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要素 |
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-超分子 #1: Active RIP2 signaling complex
超分子 | 名称: Active RIP2 signaling complex / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Receptor-interacting serine/threonine-protein kinase 2
分子 | 名称: Receptor-interacting serine/threonine-protein kinase 2 タイプ: protein_or_peptide / ID: 1 / コピー数: 12 / 光学異性体: LEVO / EC番号: non-specific serine/threonine protein kinase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 12.621438 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: TNSAGIAQQW IQSKREDIVN QMTEACLNQS LDALLSRDLI MKEDYELVST KPTRTSKVRQ LLDTTDIQGE EFAKVIVQKL KDNKQMGLQ PYPEILVVSR SPSLNLLQNK SM UniProtKB: Receptor-interacting serine/threonine-protein kinase 2 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | らせん対称体再構成法 |
試料の集合状態 | filament |
-試料調製
濃度 | 0.2 mg/mL |
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緩衝液 | pH: 7.4 |
グリッド | 材質: COPPER / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
凍結 | 凍結剤: METHANE |
-電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 撮影したグリッド数: 3 / 実像数: 3100 / 平均電子線量: 8.0 e/Å2 |
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
-画像解析
-原子モデル構築 1
精密化 | 空間: RECIPROCAL / プロトコル: RIGID BODY FIT / 温度因子: 202.7 / 当てはまり具合の基準: Rfree value |
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得られたモデル | PDB-5yrn: |