+データを開く
-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 | ||||||||||||
要素 |
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キーワード | ANTITUMOR PROTEIN / Pdcd4 / eIF4A / ribosome / 43S / translation | ||||||||||||
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 / eukaryotic translation initiation factor 3 complex, eIF3m / cap-dependent translational initiation ...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 / eukaryotic translation initiation factor 3 complex, eIF3m / cap-dependent translational initiation / IRES-dependent viral translational initiation / translation reinitiation / nuclear stress granule / RNA cap binding / eukaryotic translation initiation factor 3 complex / eukaryotic translation initiation factor 4F complex / formation of cytoplasmic translation initiation complex / cytoplasmic translational initiation / multi-eIF complex / Z-decay: degradation of maternal mRNAs by zygotically expressed factors / translation factor activity, RNA binding / mRNA cap binding / eukaryotic 43S preinitiation complex / negative regulation of JUN kinase activity / Deadenylation of mRNA / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / protein tyrosine kinase inhibitor activity / 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 endothelial cell apoptotic process / eukaryotic 48S preinitiation complex / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / IRE1-RACK1-PP2A complex / M-decay: degradation of maternal mRNAs by maternally stored factors / positive regulation of Golgi to plasma membrane protein transport / positive regulation of endodeoxyribonuclease activity / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / response to alkaloid / metal-dependent deubiquitinase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / neural crest cell differentiation / oxidized purine DNA binding / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / regulation of translational initiation / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / 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 / laminin receptor activity / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / 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 / positive regulation of mitochondrial depolarization / mammalian oogenesis stage / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / iron-sulfur cluster binding / monocyte chemotaxis / positive regulation of activated T cell proliferation / Protein hydroxylation / regulation of cell division / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / 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 / phagocytic cup / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / ribosomal small subunit binding / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction 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: 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
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 9bln.cif.gz | 2.7 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9bln.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 9bln.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
文書・要旨 | 9bln_validation.pdf.gz | 1.9 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9bln_full_validation.pdf.gz | 2 MB | 表示 | |
XML形式データ | 9bln_validation.xml.gz | 246.6 KB | 表示 | |
CIF形式データ | 9bln_validation.cif.gz | 418.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/bl/9bln ftp://data.pdbj.org/pub/pdb/validation_reports/bl/9bln | 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 (文献) 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 |
-リンク
-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) Homo sapiens (ヒト) / 参照: UniProt: Q13347 |
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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) Homo sapiens (ヒト) / 参照: UniProt: B4DXN6 |
#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) Homo sapiens (ヒト) / 参照: UniProt: Q9UBQ5 |
#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) Homo sapiens (ヒト) / 参照: UniProt: O00303, ubiquitinyl hydrolase 1 |
#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) Homo sapiens (ヒト) / 参照: UniProt: Q9Y262 |
#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) Homo sapiens (ヒト) / 参照: UniProt: Q7L2H7 |
#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) Homo sapiens (ヒト) / 参照: UniProt: O15372 |
#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) Homo sapiens (ヒト) / 参照: UniProt: O75821 |
#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) Homo sapiens (ヒト) / 参照: UniProt: Q14152 |
#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) Homo sapiens (ヒト) / 参照: UniProt: P60228 |
#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) Homo sapiens (ヒト) / 参照: UniProt: O15371 |
#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) Homo sapiens (ヒト) / 参照: UniProt: Q99613 |
+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) Homo sapiens (ヒト) |
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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) Homo sapiens (ヒト) / 参照: UniProt: P62263 |
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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) Homo sapiens (ヒト) / 遺伝子: EIF1, SUI1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P41567 |
#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) Homo sapiens (ヒト) / 参照: UniProt: P63244 |
#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) Homo sapiens (ヒト) / 参照: UniProt: P62979 |
#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) Homo sapiens (ヒト) / 遺伝子: EIF4A1, DDX2A, EIF4A / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P60842, RNA helicase |
#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) Homo sapiens (ヒト) / 遺伝子: PDCD4, H731 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: Q53EL6 |
-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 |
-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: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli (大腸菌) |
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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
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) |
-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 |