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基本情報
登録情報 | データベース: PDB / ID: 9kv7 | |||||||||
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タイトル | Cryo-EM structure of mouse RIPK1-DD filament | |||||||||
![]() | Receptor-interacting serine/threonine-protein kinase 1 | |||||||||
![]() | IMMUNE SYSTEM / RIPK1 / death domain / 568-656 / dimerization | |||||||||
機能・相同性 | ![]() TNF signaling / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / TNFR1-induced proapoptotic signaling / Caspase activation via Death Receptors in the presence of ligand / RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / ripoptosome assembly / positive regulation of miRNA processing ...TNF signaling / Regulation by c-FLIP / CASP8 activity is inhibited / Dimerization of procaspase-8 / TNFR1-induced proapoptotic signaling / Caspase activation via Death Receptors in the presence of ligand / RIPK1-mediated regulated necrosis / TRIF-mediated programmed cell death / ripoptosome assembly / positive regulation of miRNA processing / positive regulation of interleukin-6-mediated signaling pathway / ripoptosome assembly involved in necroptotic process / TNFR1-induced NF-kappa-B signaling pathway / death domain binding / Regulation of TNFR1 signaling / Regulation of necroptotic cell death / Ovarian tumor domain proteases / IKK complex recruitment mediated by RIP1 / peptidyl-serine autophosphorylation / ripoptosome / programmed necrotic cell death / positive regulation of macrophage differentiation / T cell apoptotic process / TRP channels / necroptotic signaling pathway / Ub-specific processing proteases / death-inducing signaling complex / positive regulation of necroptotic process / negative regulation of necroptotic process / positive regulation of tumor necrosis factor-mediated signaling pathway / death receptor binding / positive regulation of extrinsic apoptotic signaling pathway / regulation of reactive oxygen species metabolic process / necroptotic process / positive regulation of phosphorylation / extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of execution phase of apoptosis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / signaling adaptor activity / negative regulation of canonical NF-kappaB signal transduction / tumor necrosis factor-mediated signaling pathway / negative regulation of extrinsic apoptotic signaling pathway / positive regulation of interleukin-8 production / positive regulation of JNK cascade / protein catabolic process / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of NF-kappaB transcription factor activity / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / positive regulation of protein phosphorylation / positive regulation of inflammatory response / positive regulation of tumor necrosis factor production / cellular response to tumor necrosis factor / positive regulation of neuron apoptotic process / protein autophosphorylation / amyloid fibril formation / positive regulation of canonical NF-kappaB signal transduction / non-specific serine/threonine protein kinase / receptor complex / protein kinase activity / positive regulation of MAPK cascade / intracellular signal transduction / positive regulation of apoptotic process / inflammatory response / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / ubiquitin protein ligase binding / negative regulation of apoptotic process / protein-containing complex binding / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / mitochondrion / ATP binding 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: 3.02 Å | |||||||||
![]() | Zhang, H. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: RIPK1 senses S-adenosylmethionine scarcity to drive cell death and inflammation. 著者: Zezhao Chen / Xiaosong Gu / Hongbo Chen / Huijing Zhang / Jianping Liu / Xiaohua Yang / Yuping Cai / Mengmeng Zhang / Lingjie Yan / Yuanxin Yang / Bing Shan / Zheng-Jiang Zhu / Yixiao Zhang / ...著者: Zezhao Chen / Xiaosong Gu / Hongbo Chen / Huijing Zhang / Jianping Liu / Xiaohua Yang / Yuping Cai / Mengmeng Zhang / Lingjie Yan / Yuanxin Yang / Bing Shan / Zheng-Jiang Zhu / Yixiao Zhang / Jinyang Gu / Daichao Xu / ![]() 要旨: The capacity of cells to sense and respond to nutrient availability is essential for metabolic homeostasis. Failure in this process may cause cell death and associated diseases. While nutrient ...The capacity of cells to sense and respond to nutrient availability is essential for metabolic homeostasis. Failure in this process may cause cell death and associated diseases. While nutrient sensing in metabolic pathways is well understood, the mechanisms linking nutrient signals to cell death remain unclear. Here, we show that RIPK1, a key mediator of cell death and inflammation, senses methionine and its metabolite, S-adenosylmethionine (SAM), to dictate cell survival and death. SAM-mediated symmetrical dimethylation at RIPK1 Arg606 by PRMT5 functions as a physiological protective brake against RIPK1 activation. Metabolic perturbations, such as methionine restriction or disrupted one-carbon flux, reduce SAM levels and unmask Arg606, promoting RIPK1 self-association and trans-activation, thereby triggering apoptosis and inflammation. Thus, RIPK1 is a physiological SAM sensor linking methionine and one-carbon metabolism to the control of life-or-death decisions. Our findings suggest that RIPK1 could be a potential target for diseases associated with disrupted SAM availability. | |||||||||
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構造の表示
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 | ![]() | 361.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 296.6 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 | ![]() | 1.5 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.5 MB | 表示 | |
XML形式データ | ![]() | 53 KB | 表示 | |
CIF形式データ | ![]() | 83.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 62587MC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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: 13810.670 Da / 分子数: 23 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() 参照: UniProt: Q60855, non-specific serine/threonine protein kinase Has protein modification | 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: FILAMENT / 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: Receptor-interacting serine/threonine-protein kinase 1 タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.001017 MDa / 実験値: NO |
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-PROPANE |
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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: TFS KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2400 nm / 最小 デフォーカス(公称値): 1400 nm |
撮影 | 電子線照射量: 49.41 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
EMソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874 / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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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: 139.82 ° / 軸方向距離/サブユニット: 4.96 Å / らせん対称軸の対称性: C1 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.02 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 988646 / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
拘束条件 |
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