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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: 9rpv | |||||||||||||||
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| タイトル | Structure of the ZAK-bound human disome | |||||||||||||||
要素 |
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キーワード | RIBOSOME / ZAK / collision / RSR / quality control | |||||||||||||||
| 機能・相同性 | 機能・相同性情報positive regulation of mitotic DNA damage checkpoint / negative regulation of stress-activated protein kinase signaling cascade / stalled ribosome sensor activity / negative regulation of translation in response to endoplasmic reticulum stress / GCN2-mediated signaling / cell death / mitogen-activated protein kinase kinase kinase / endothelial cell differentiation / JUN kinase kinase kinase activity / embryonic brain development ...positive regulation of mitotic DNA damage checkpoint / negative regulation of stress-activated protein kinase signaling cascade / stalled ribosome sensor activity / negative regulation of translation in response to endoplasmic reticulum stress / GCN2-mediated signaling / cell death / mitogen-activated protein kinase kinase kinase / endothelial cell differentiation / JUN kinase kinase kinase activity / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of formation of translation preinitiation complex / axial mesoderm development / positive regulation of programmed cell death / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of ubiquitin-protein transferase activity / protein-DNA complex disassembly / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / positive regulation of DNA-templated transcription initiation / alpha-beta T cell differentiation / stress-activated protein kinase signaling cascade / TNFR1-mediated ceramide production / positive regulation of DNA binding / positive regulation of DNA damage response, signal transduction by p53 class mediator / regulation of mitotic metaphase/anaphase transition / GAIT complex / negative regulation of RNA splicing / embryonic digit morphogenesis / cellular response to UV-B / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / limb development / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / p38MAPK cascade / ion channel inhibitor activity / laminin receptor activity / protein kinase A binding / homeostatic process / pigmentation / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization / Translation initiation complex formation / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / TFIID-class transcription factor complex binding / fibroblast growth factor binding / male meiosis I / regulation of lipid metabolic process / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / TOR signaling / positive regulation of GTPase activity / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / iron-sulfur cluster binding / regulation of cell division / Peptide chain elongation / cellular response to ethanol / pyroptotic inflammatory response / Selenocysteine synthesis 類似検索 - 分子機能 | |||||||||||||||
| 生物種 | Homo sapiens (ヒト) | |||||||||||||||
| 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: 2.35 Å | |||||||||||||||
データ登録者 | Niu, S. / Beckmann, R. | |||||||||||||||
| 資金援助 | European Union, 1件
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引用 | ジャーナル: Nature / 年: 2026タイトル: ZAK activation at the collided ribosome. 著者: Vienna L Huso / Shuangshuang Niu / Marco A Catipovic / James A Saba / Timo Denk / Eugene Park / Jingdong Cheng / Otto Berninghausen / Thomas Becker / Rachel Green / Roland Beckmann / ![]() 要旨: Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK. ...Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK. Despite the critical role of ZAK during cellular stress, a mechanistic and structural understanding of ZAK-ribosome interactions and how these lead to activation remain elusive. Here we combine biochemistry and cryo-electron microscopy to discover distinct ZAK-ribosome interactions required for constitutive recruitment and for activation. We find that upon induction of ribosome collisions, interactions between ZAK and the ribosomal protein RACK1 enable its activation by dimerization of its SAM domains at the collision interface. Furthermore, we discover how this process is negatively regulated by the ribosome-binding protein SERBP1 to prevent constitutive ZAK activation. Characterization of novel SAM variants as well as a known pathogenic variant of the SAM domain of ZAK supports a key role of the SAM domain in regulating kinase activity on and off the ribosome, with some mutants bypassing the ribosome requirement for ZAK activation. Collectively, our data provide a mechanistic blueprint of the kinase activity of ZAK at the collided ribosome interface. | |||||||||||||||
| 履歴 |
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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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 | 9rpv.cif.gz | 10.5 MB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb9rpv.ent.gz | 表示 | PDB形式 | |
| PDBx/mmJSON形式 | 9rpv.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
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/rp/9rpv ftp://data.pdbj.org/pub/pdb/validation_reports/rp/9rpv | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 54172MC ![]() 9rsxC ![]() 54191 C: 同じ文献を引用 ( 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 |
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リンク
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集合体
| 登録構造単位 | ![]()
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| 1 |
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要素
+RNA鎖 , 7種, 8分子 A4A5B4B5D4E5L7M7
+タンパク質 , 8種, 12分子 E4LILmMmN1N2ReSeRfshRgSg
+28S rRNA of the ... , 2種, 2分子 L5M5
+5.8S rRNA of the ... , 2種, 2分子 L8M8
+60S ribosomal protein ... , 38種, 68分子 LALBLCMCLDMDLGMGLHMHLJMJLMMMLNMNLOMOLPMPLQMQLRMRLSMSLTMTLUMU...
+Large ribosomal subunit protein ... , 10種, 14分子 LEMELFMFLLMLLjMjMAMBMaMbMoMr
+Small ribosomal subunit protein ... , 3種, 4分子 RARESERV
+40S ribosomal protein ... , 29種, 56分子 RBSBRCSCRDSDRFSFRGSGRHSHRISIRJSJRKSKRLSLRMSfRNSNROSORPSPRQSQ...
+18S rRNA of the ... , 2種, 2分子 S2S3
+非ポリマー , 3種, 838分子 




+詳細
-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 |
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試料調製
| 構成要素 | 名称: ZAK-bound human disome / タイプ: RIBOSOME Entity ID: #2, #4, #6-#7, #53, #9, #54-#56, #13-#18, #57, #20-#35, #58-#59, #38-#47, #60, #49, #61, #51, #62-#63, #65-#87, #89-#91, #93-#96, #99, #1, #3, #5, #8, #10-#12, #19, #36-#37, #48, #50, #52, ...Entity ID: #2, #4, #6-#7, #53, #9, #54-#56, #13-#18, #57, #20-#35, #58-#59, #38-#47, #60, #49, #61, #51, #62-#63, #65-#87, #89-#91, #93-#96, #99, #1, #3, #5, #8, #10-#12, #19, #36-#37, #48, #50, #52, #98, #101, #88, #97, #64, #92 由来: NATURAL |
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| 分子量 | 実験値: NO |
| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 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: 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: FIELD EMISSION GUN / 加速電圧: 300 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): 3500 nm / 最小 デフォーカス(公称値): 500 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) |
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解析
| EMソフトウェア |
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| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
| 3次元再構成 | 解像度: 2.35 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 139996 詳細: 123142 particles from the stalled 80S map; 139,996 particles from the collided 80S map. 対称性のタイプ: POINT |
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万見について




Homo sapiens (ヒト)
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FIELD EMISSION GUN