+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-12633 | |||||||||
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タイトル | Mammalian pre-termination 80S ribosome with Empty-A site bound by Blasticidin S | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 Formation of the ternary complex, and subsequently, the 43S complex / Formation of a pool of free 40S subunits / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Translation initiation complex formation / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit ...Formation of the ternary complex, and subsequently, the 43S complex / Formation of a pool of free 40S subunits / SRP-dependent cotranslational protein targeting to membrane / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Translation initiation complex formation / Ribosomal scanning and start codon recognition / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / Major pathway of rRNA processing in the nucleolus and cytosol / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Formation of a pool of free 40S subunits / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / regulation of G1 to G0 transition / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / G1 to G0 transition / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / ribosomal small subunit export from nucleus / translation regulator activity / cellular response to actinomycin D / 90S preribosome / 小胞体 / gastrulation / cytosolic ribosome / MDM2/MDM4 family protein binding / translation initiation factor binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / rescue of stalled ribosome / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / negative regulation of ubiquitin-dependent protein catabolic process / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA / positive regulation of translation / positive regulation of apoptotic signaling pathway / small-subunit processome / protein kinase C binding / positive regulation of protein-containing complex assembly / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / cytoplasmic ribonucleoprotein granule / spindle / rRNA processing / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit rRNA binding / positive regulation of canonical Wnt signaling pathway / rhythmic process / リボソーム生合成 / ribosome binding / regulation of translation / heparin binding / 5S rRNA binding / large ribosomal subunit rRNA binding / small ribosomal subunit / cytosolic small ribosomal subunit / postsynapse / perikaryon / cytosolic large ribosomal subunit / cytoplasmic translation / ミトコンドリア内膜 / tRNA binding / postsynaptic density / 細胞分化 / protein stabilization / rRNA binding / リボソーム / structural constituent of ribosome / ribonucleoprotein complex / 翻訳 (生物学) / positive regulation of protein phosphorylation / 細胞周期 / 細胞分裂 / DNA修復 / mRNA binding / 中心体 / apoptotic process / シナプス / ubiquitin protein ligase binding / 樹状突起 / positive regulation of cell population proliferation / positive regulation of gene expression / 核小体 / negative regulation of apoptotic process / perinuclear region of cytoplasm / ゴルジ体 / negative regulation of transcription by RNA polymerase II / 小胞体 / DNA binding 類似検索 - 分子機能 | |||||||||
生物種 | Oryctolagus cuniculus (ウサギ) / Rabbit (ウサギ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.13 Å | |||||||||
データ登録者 | Powers KT / Yadav SKN / Bufton JC / Schaffitzel C | |||||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: Nucleic Acids Res / 年: 2021 タイトル: Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA. 著者: Kyle T Powers / Flint Stevenson-Jones / Sathish K N Yadav / Beate Amthor / Joshua C Bufton / Ufuk Borucu / Dakang Shen / Jonas P Becker / Daria Lavysh / Matthias W Hentze / Andreas E Kulozik ...著者: Kyle T Powers / Flint Stevenson-Jones / Sathish K N Yadav / Beate Amthor / Joshua C Bufton / Ufuk Borucu / Dakang Shen / Jonas P Becker / Daria Lavysh / Matthias W Hentze / Andreas E Kulozik / Gabriele Neu-Yilik / Christiane Schaffitzel / 要旨: Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding ...Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3'CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor 1 (eRF1), it interferes with eRF1's accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_12633.map.gz | 15.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-12633-v30.xml emd-12633.xml | 95.6 KB 95.6 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_12633_fsc.xml | 10.6 KB | 表示 | FSCデータファイル |
画像 | emd_12633.png | 121.8 KB | ||
マスクデータ | emd_12633_msk_1.map | 103 MB | マスクマップ | |
その他 | emd_12633_half_map_1.map.gz emd_12633_half_map_2.map.gz | 80.7 MB 80.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-12633 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-12633 | HTTPS FTP |
-関連構造データ
-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_12633.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | emd_12633_msk_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_12633_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: #2
ファイル | emd_12633_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Mammalian pre-termination 80S ribosome with Empty-A site bound by...
+超分子 #1: Mammalian pre-termination 80S ribosome with Empty-A site bound by...
+分子 #1: L8
+分子 #2: uL3
+分子 #3: 60S ribosomal protein L4
+分子 #4: 60S ribosomal protein L5
+分子 #5: 60S ribosomal protein L6
+分子 #6: uL30
+分子 #7: 60S ribosomal protein L7a
+分子 #8: L9
+分子 #9: 60S ribosomal protein L10
+分子 #10: Ribosomal protein L11
+分子 #11: L13
+分子 #12: Ribosomal protein L14
+分子 #13: Ribosomal protein L15
+分子 #14: L13a
+分子 #15: L17
+分子 #16: Ribosomal_L18e/L15P domain-containing protein
+分子 #17: 60S ribosomal protein L19
+分子 #18: L18a
+分子 #19: eL21
+分子 #20: 60S ribosomal protein L22
+分子 #21: eL14
+分子 #22: 60S ribosomal protein L24-like protein
+分子 #23: uL23
+分子 #24: Ribosomal protein L26
+分子 #25: 60S ribosomal protein L27
+分子 #26: uL15
+分子 #27: 60S ribosomal protein L29
+分子 #28: eL30
+分子 #29: eL31
+分子 #30: eL32
+分子 #31: eL33
+分子 #32: 60S ribosomal protein L34
+分子 #33: uL29
+分子 #34: 60S ribosomal protein L36
+分子 #35: Ribosomal protein L37
+分子 #36: L38
+分子 #37: ribosomal protein eL39
+分子 #38: 60S ribosomal protein L40
+分子 #39: 60s ribosomal protein l41
+分子 #40: LOW QUALITY PROTEIN: 60S ribosomal protein L36a
+分子 #41: ribosomal protein eL43
+分子 #42: eL28
+分子 #43: 60S acidic ribosomal protein P0
+分子 #44: L12
+分子 #45: 40S ribosomal protein SA
+分子 #46: 40S ribosomal protein S3a
+分子 #47: 40S ribosomal protein S2
+分子 #48: 40S ribosomal protein S3
+分子 #49: S4
+分子 #50: Ribosomal protein S5
+分子 #51: 40S ribosomal protein S6
+分子 #52: ribosomal protein eS7
+分子 #53: 40S ribosomal protein S8
+分子 #54: 40S ribosomal protein S9
+分子 #55: S10_plectin domain-containing protein
+分子 #56: 40S ribosomal protein S11
+分子 #57: 40S ribosomal protein S12
+分子 #58: ribosomal protein uS15
+分子 #59: S14
+分子 #60: 40S ribosomal protein uS19
+分子 #61: Rps16 protein
+分子 #62: S17
+分子 #63: ribosomal protein uS13
+分子 #64: S19
+分子 #65: Ribosomal_S10 domain-containing protein
+分子 #66: S21
+分子 #67: Ribosomal protein S15a
+分子 #68: Ribosomal protein S23
+分子 #69: 40S ribosomal protein S24
+分子 #70: 40S ribosomal protein S25
+分子 #71: 40S ribosomal protein S26
+分子 #72: 40S ribosomal protein S27
+分子 #73: 40S ribosomal protein S28
+分子 #74: ribosomal protein uS14
+分子 #75: 40S ribosomal protein S30
+分子 #76: S27a
+分子 #77: ribosomal protein RACK1
+分子 #78: Sec61Beta
+分子 #79: P-Site tRNA
+分子 #80: 28S ribosomal RNA+BlaS
+分子 #81: 5S ribosomal RNA
+分子 #82: 5.8S ribosomal RNA
+分子 #83: 18S ribosomal RNA
+分子 #84: mRNA
+分子 #85: MAGNESIUM ION
+分子 #86: ZINC ION
+分子 #87: BLASTICIDIN S
-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
濃度 | 0.63 mg/mL |
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緩衝液 | pH: 7.4 詳細: 50 mM HEPES pH 7.4 100 mM KOAc 5 mM Mg(Oac)2 1mM DTT |
グリッド | モデル: Quantifoil R2/2 / 材質: COPPER / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 30 sec. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 70 % / チャンバー内温度: 288.15 K / 装置: LEICA EM GP 詳細: 30s sample incubation on grid followed by 1.1s blotting time.. |
詳細 | 165nM (OD260nm~10.5) |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 100.0 µm / 最大 デフォーカス(補正後): 2.0 µm / 最小 デフォーカス(補正後): 0.4 µm / 倍率(補正後): 79000 / 照射モード: OTHER / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
詳細 | Collected in super-resolution mode (0.675A pixel size) |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 撮影したグリッド数: 1 / 実像数: 3500 / 平均露光時間: 8.0 sec. / 平均電子線量: 41.92 e/Å2 |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |