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万見- EMDB-44671: The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex -
+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-44671 | ||||||||||||
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タイトル | The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | Pdcd4 / eIF4A / ribosome / 43S / translation / ANTITUMOR PROTEIN | ||||||||||||
機能・相同性 | 機能・相同性情報 epithelial to mesenchymal transition involved in cardiac fibroblast development / negative regulation of myofibroblast differentiation / negative regulation of vascular associated smooth muscle cell differentiation / positive regulation of mRNA binding / positive regulation of mRNA cis splicing, via spliceosome / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m ...epithelial to mesenchymal transition involved in cardiac fibroblast development / negative regulation of myofibroblast differentiation / negative regulation of vascular associated smooth muscle cell differentiation / positive regulation of mRNA binding / positive regulation of mRNA cis splicing, via spliceosome / viral translational termination-reinitiation / eukaryotic translation initiation factor 3 complex, eIF3e / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / cap-dependent translational initiation / eukaryotic translation initiation factor 3 complex, eIF3m / IRES-dependent viral translational initiation / translation reinitiation / RNA cap binding / nuclear stress granule / eukaryotic translation initiation factor 4F complex / eukaryotic translation initiation factor 3 complex / formation of cytoplasmic translation initiation complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / multi-eIF complex / cytoplasmic translational initiation / translation factor activity, RNA binding / mRNA cap binding / eukaryotic 43S preinitiation complex / negative regulation of JUN kinase activity / Deadenylation of mRNA / : / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of endothelial cell apoptotic process / eukaryotic 48S preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / M-decay: degradation of maternal mRNAs by maternally stored factors / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / response to alkaloid / metal-dependent deubiquitinase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / NF-kappaB complex / neural crest cell differentiation / ubiquitin-like protein conjugating enzyme binding / regulation of translational initiation / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / laminin receptor activity / pigmentation / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / positive regulation of vascular associated smooth muscle cell apoptotic process / Translation initiation complex formation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / iron-sulfur cluster binding / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation / regulation of cell division / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / negative regulation of vascular associated smooth muscle cell proliferation / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / cysteine-type endopeptidase activator activity involved in apoptotic process / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response / ribosomal small subunit binding / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | ||||||||||||
データ登録者 | Brito Querido J / Sokabe M / Diaz-Lopez I / Gordiyenko Y / Zuber P / Yifei D / Albacete-Albacete L / Ramakrishnan V / S Fraser C | ||||||||||||
資金援助 | 英国, スイス, 3件
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引用 | ジャーナル: Nat Commun / 年: 2024 タイトル: Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit. 著者: Jailson Brito Querido / Masaaki Sokabe / Irene Díaz-López / Yuliya Gordiyenko / Philipp Zuber / Yifei Du / Lucas Albacete-Albacete / V Ramakrishnan / Christopher S Fraser / 要旨: Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including ...Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5' UTR of mRNA. | ||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_44671.map.gz | 40.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-44671-v30.xml emd-44671.xml | 79.2 KB 79.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_44671.png | 55.2 KB | ||
マスクデータ | emd_44671_msk_1.map | 244.1 MB | マスクマップ | |
Filedesc metadata | emd-44671.cif.gz | 18.1 KB | ||
その他 | emd_44671_additional_1.map.gz emd_44671_additional_2.map.gz emd_44671_additional_3.map.gz emd_44671_half_map_1.map.gz emd_44671_half_map_2.map.gz | 39.7 MB 227 MB 226.9 MB 194.6 MB 194.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-44671 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44671 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_44671_validation.pdf.gz | 1 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_44671_full_validation.pdf.gz | 1 MB | 表示 | |
XML形式データ | emd_44671_validation.xml.gz | 16 KB | 表示 | |
CIF形式データ | emd_44671_validation.cif.gz | 18.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44671 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44671 | HTTPS FTP |
-関連構造データ
関連構造データ | 9blnMC 9bkdC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_44671.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.025 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_44671_msk_1.map | ||||||||||||
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密度ヒストグラム |
-追加マップ: Pdcd4-40S-eIf3-eIF1 PostProcess
ファイル | emd_44671_additional_1.map | ||||||||||||
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注釈 | Pdcd4-40S-eIf3-eIF1 PostProcess | ||||||||||||
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密度ヒストグラム |
-追加マップ: Pdcd4-40S-eIf3-eIF1 3D Refinement
ファイル | emd_44671_additional_2.map | ||||||||||||
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注釈 | Pdcd4-40S-eIf3-eIF1 3D Refinement | ||||||||||||
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密度ヒストグラム |
-追加マップ: #1
ファイル | emd_44671_additional_3.map | ||||||||||||
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_44671_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_44671_half_map_2.map | ||||||||||||
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密度ヒストグラム |
-試料の構成要素
+全体 : Pdcd4-40S-eIF4A-eIF3-eIF1 complex
+超分子 #1: Pdcd4-40S-eIF4A-eIF3-eIF1 complex
+分子 #1: Eukaryotic translation initiation factor 3 subunit I
+分子 #2: Eukaryotic translation initiation factor 3 subunit B
+分子 #3: Eukaryotic translation initiation factor 3 subunit K
+分子 #4: Eukaryotic translation initiation factor 3 subunit F
+分子 #5: Eukaryotic translation initiation factor 3 subunit L
+分子 #6: Eukaryotic translation initiation factor 3 subunit M
+分子 #7: Eukaryotic translation initiation factor 3 subunit H
+分子 #8: Small ribosomal subunit protein eS32
+分子 #10: Small ribosomal subunit protein uS17
+分子 #11: Small ribosomal subunit protein eS4, X isoform
+分子 #12: Small ribosomal subunit protein uS4
+分子 #13: Small ribosomal subunit protein uS12
+分子 #14: Small ribosomal subunit protein eS30
+分子 #15: Small ribosomal subunit protein eS7
+分子 #16: Small ribosomal subunit protein eS27
+分子 #17: Small ribosomal subunit protein uS15
+分子 #18: Small ribosomal subunit protein uS8
+分子 #19: Small ribosomal subunit protein eS21
+分子 #20: Small ribosomal subunit protein uS5
+分子 #21: Small ribosomal subunit protein eS17
+分子 #22: Small ribosomal subunit protein uS2
+分子 #23: Small ribosomal subunit protein eS1
+分子 #24: 40S ribosomal protein S14
+分子 #25: Small ribosomal subunit protein eS26
+分子 #26: Small ribosomal subunit protein eS8
+分子 #27: Small ribosomal subunit protein eS6
+分子 #28: Small ribosomal subunit protein eS24
+分子 #29: Small ribosomal subunit protein uS7
+分子 #30: Eukaryotic translation initiation factor 1
+分子 #31: Small ribosomal subunit protein uS9
+分子 #32: Small ribosomal subunit protein uS3
+分子 #33: Small ribosomal subunit protein eS10
+分子 #34: Small ribosomal subunit protein uS19
+分子 #35: Receptor of activated protein C kinase 1
+分子 #36: Small ribosomal subunit protein eS19
+分子 #37: Small ribosomal subunit protein eS25
+分子 #38: Small ribosomal subunit protein uS13
+分子 #39: Small ribosomal subunit protein uS10
+分子 #40: Small ribosomal subunit protein uS14
+分子 #41: Ubiquitin-40S ribosomal protein S27a
+分子 #42: Eukaryotic initiation factor 4A-I
+分子 #43: Small ribosomal subunit protein eS12
+分子 #44: Small ribosomal subunit protein eS28
+分子 #45: Eukaryotic translation initiation factor 3 subunit G
+分子 #46: Programmed cell death protein 4
+分子 #47: Eukaryotic translation initiation factor 3 subunit A
+分子 #48: Eukaryotic translation initiation factor 3 subunit E
+分子 #49: Eukaryotic translation initiation factor 3 subunit D
+分子 #50: Eukaryotic translation initiation factor 3 subunit C
+分子 #9: rRNA
+分子 #51: MAGNESIUM ION
+分子 #52: POTASSIUM ION
+分子 #53: SPERMIDINE
+分子 #54: ZINC ION
+分子 #55: ACETIC ACID
-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 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.4 |
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グリッド | モデル: Quantifoil / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 45 sec. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 4 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOCONTINUUM (6k x 4k) 平均電子線量: 25.0 e/Å2 |
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: OTHER / 撮影モード: OTHER / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 8515 |
初期 角度割当 | タイプ: OTHER |
最終 角度割当 | タイプ: OTHER |