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基本情報
登録情報 | データベース: PDB / ID: 9bln | ||||||||||||
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タイトル | The structure of human Pdcd4 bound to the 40S-eIF4A-eIF3-eIF1 complex | ||||||||||||
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![]() | ANTITUMOR PROTEIN / Pdcd4 / eIF4A / ribosome / 43S / translation | ||||||||||||
機能・相同性 | ![]() 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 / viral translational termination-reinitiation / negative regulation of JUN kinase activity / eukaryotic translation initiation factor 3 complex, eIF3e / cap-dependent translational initiation / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / 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 / viral translational termination-reinitiation / negative regulation of JUN kinase activity / eukaryotic translation initiation factor 3 complex, eIF3e / cap-dependent translational initiation / Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S / eukaryotic translation initiation factor 3 complex, eIF3m / IRES-dependent viral translational initiation / translation reinitiation / nuclear stress granule / eukaryotic translation initiation factor 3 complex / RNA cap binding / eukaryotic translation initiation factor 4F complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / multi-eIF complex / translation factor activity, RNA binding / eukaryotic 43S preinitiation complex / mRNA cap binding / Deadenylation of mRNA / eukaryotic 48S preinitiation complex / M-decay: degradation of maternal mRNAs by maternally stored factors / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / metal-dependent deubiquitinase activity / supercoiled DNA binding / neural crest cell differentiation / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / positive regulation of ubiquitin-protein transferase activity / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / regulation of translational initiation / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / positive regulation of vascular associated smooth muscle cell apoptotic process / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / protein kinase A binding / pigmentation / Ribosomal scanning and start codon recognition / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / monocyte chemotaxis / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / Protein hydroxylation / TOR signaling / BH3 domain binding / regulation of cell division / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / negative regulation of vascular associated smooth muscle cell proliferation / cellular response to ethanol / iron-sulfur cluster binding / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal small subunit binding / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / Response of EIF2AK4 (GCN2) to amino acid deficiency / positive regulation of signal transduction by p53 class mediator / negative regulation of ubiquitin-dependent protein catabolic process / positive regulation of endothelial cell apoptotic process / SRP-dependent cotranslational protein targeting to membrane / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() | ||||||||||||
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: 3.9 Å | ||||||||||||
![]() | 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 | ![]() ![]()
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![]() | ![]() 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
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 | ![]() | 2.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.9 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2 MB | 表示 | |
XML形式データ | ![]() | 246.6 KB | 表示 | |
CIF形式データ | ![]() | 418.2 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 | ![]() 44671MC ![]() 9bkdC 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 ![]() |
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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
-Eukaryotic translation initiation factor 3 subunit ... , 12種, 12分子 XU34568ouvxy
#1: タンパク質 | 分子量: 36543.773 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#2: タンパク質 | 分子量: 77328.625 Da / 分子数: 1 / 由来タイプ: 天然 / 詳細: Protein / 由来: (天然) ![]() |
#3: タンパク質 | 分子量: 25083.619 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#4: タンパク質 | 分子量: 37593.645 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#5: タンパク質 | 分子量: 66803.734 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#6: タンパク質 | 分子量: 42555.832 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#7: タンパク質 | 分子量: 39979.277 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#45: タンパク質 | 分子量: 35662.016 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#47: タンパク質 | 分子量: 166903.781 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#48: タンパク質 | 分子量: 52281.633 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#49: タンパク質 | 分子量: 64060.758 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#50: タンパク質 | 分子量: 105503.945 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+Small ribosomal subunit protein ... , 31種, 31分子 9BCDEFGHIJKLMNOQRSTVYZabdefhimn
-RNA鎖 , 1種, 1分子 A
#9: RNA鎖 | 分子量: 555109.000 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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-タンパク質 , 6種, 6分子 PWcklp
#24: タンパク質 | 分子量: 16302.772 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#30: タンパク質 | 分子量: 12752.498 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#35: タンパク質 | 分子量: 35115.652 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#41: タンパク質 | 分子量: 18004.041 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#42: タンパク質 | 分子量: 44317.922 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#46: タンパク質 | 分子量: 52224.215 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-非ポリマー , 5種, 112分子 








#51: 化合物 | ChemComp-MG / #52: 化合物 | ChemComp-K / #53: 化合物 | ChemComp-SPD / | #54: 化合物 | #55: 化合物 | ChemComp-ACY / | |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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Has protein modification | Y |
-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: Pdcd4-40S-eIF4A-eIF3-eIF1 complex / タイプ: COMPLEX / Entity ID: #2, #1, #3-#50 / 由来: RECOMBINANT |
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分子量 | 値: 2.2 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: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 4 K |
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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: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: OTHER / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 25 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOCONTINUUM (6k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 8515 / 対称性のタイプ: POINT |