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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: EMDB / ID: EMD-2660 | |||||||||
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タイトル | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine | |||||||||
![]() | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine | |||||||||
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![]() | Plasmodium falciparum / 80S ribosome / Cryo-EM / emetine | |||||||||
機能・相同性 | ![]() RMTs methylate histone arginines / Major pathway of rRNA processing in the nucleolus and cytosol / Protein methylation / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs ...RMTs methylate histone arginines / Major pathway of rRNA processing in the nucleolus and cytosol / Protein methylation / Translesion synthesis by REV1 / Recognition of DNA damage by PCNA-containing replication complex / Translesion Synthesis by POLH / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / Metalloprotease DUBs / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Dual Incision in GG-NER / Formation of TC-NER Pre-Incision Complex / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / ER Quality Control Compartment (ERQC) / Iron uptake and transport / L13a-mediated translational silencing of Ceruloplasmin expression / SRP-dependent cotranslational protein targeting to membrane / Translation initiation complex formation / Formation of a pool of free 40S subunits / Formation of the ternary complex, and subsequently, the 43S complex / Ribosomal scanning and start codon recognition / GTP hydrolysis and joining of the 60S ribosomal subunit / Negative regulators of DDX58/IFIH1 signaling / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Aggrephagy / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Orc1 removal from chromatin / CDK-mediated phosphorylation and removal of Cdc6 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / KEAP1-NFE2L2 pathway / UCH proteinases / Ub-specific processing proteases / Neddylation / MAPK6/MAPK4 signaling / Antigen processing: Ubiquitination & Proteasome degradation / ABC-family proteins mediated transport / AUF1 (hnRNP D0) binds and destabilizes mRNA / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / protein-RNA complex assembly / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA / ribosomal large subunit biogenesis / maturation of SSU-rRNA / small-subunit processome / positive regulation of apoptotic signaling pathway / maintenance of translational fidelity / ribosomal large subunit assembly / mRNA 5'-UTR binding / modification-dependent protein catabolic process / rRNA processing / large ribosomal subunit / protein tag activity / ribosome biogenesis / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / large ribosomal subunit rRNA binding / ubiquitin-dependent protein catabolic process / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / ubiquitin protein ligase binding / nucleolus / mitochondrion / RNA binding / zinc ion binding / nucleus / metal ion binding / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / ネガティブ染色法 / 解像度: 3.2 Å | |||||||||
![]() | Wong W / Bai XC / Brown A / Fernandez IS / Hanssen E / Condron M / Tan YH / Baum J / Scheres SHW | |||||||||
![]() | ![]() タイトル: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine. 著者: Wilson Wong / Xiao-chen Bai / Alan Brown / Israel S Fernandez / Eric Hanssen / Melanie Condron / Yan Hong Tan / Jake Baum / Sjors H W Scheres / ![]() ![]() 要旨: Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as ...Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies. Antibiotics that inhibit protein translation are promising candidates for repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with emetine at 3.2 Å resolution. Emetine is an anti-protozoan drug used in the treatment of ameobiasis that also displays potent anti-malarial activity. Emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin, thereby delivering its therapeutic effect by blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes an antibiotic bound to any ribosome at atomic resolution, this establishes cryo-EM as a powerful tool for screening and guiding the design of drugs that target parasite translation machinery. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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 | ![]() | 166.7 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 10.8 KB 10.8 KB | 表示 表示 | ![]() |
画像 | ![]() | 344.1 KB | ||
その他 | ![]() ![]() | 140.4 MB 140.3 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 392.8 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 392.3 KB | 表示 | |
XML形式データ | ![]() | 6.9 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 | ![]() 3j79MC ![]() 3j7aMC ![]() 6okkMC ![]() 2661C 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 ( |
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類似構造データ | |
電子顕微鏡画像生データ | ![]() Data size: 1.2 TB Data #1: Unaligned multi-frame micrographs [micrographs - multiframe] Data #2: Frame averaged micrographs [micrographs - single frame] Data #3: Processed shiny particles [picked particles - multiframe - processed]) |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.34 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
-添付マップデータ: emd 2660 half map 1.map
ファイル | emd_2660_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 |
-添付マップデータ: emd 2660 half map 2.map
ファイル | emd_2660_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 |
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試料の構成要素
-全体 : Plasmodium falciparum 80S ribosome bound to the anti-protozoan dr...
全体 | 名称: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine |
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要素 |
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-超分子 #1000: Plasmodium falciparum 80S ribosome bound to the anti-protozoan dr...
超分子 | 名称: Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine タイプ: sample / ID: 1000 / Number unique components: 2 |
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分子量 | 実験値: 4.2 MDa / 理論値: 4.2 MDa |
-超分子 #1: Plasmodium falciparum 80S ribosome bound to the anti- protozoan d...
超分子 | 名称: Plasmodium falciparum 80S ribosome bound to the anti- protozoan drug emetine タイプ: complex / ID: 1 詳細: the anti-protozoan drug emetine was bound to the Plasmodium falciparum 80S ribosome 組換発現: No / Ribosome-details: ribosome-eukaryote: ALL |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 実験値: 4.2 MDa / 理論値: 4.2 MDa |
-分子 #1: emetine
分子 | 名称: emetine / タイプ: ligand / ID: 1 / 組換発現: No |
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由来(天然) | 生物種: synthetic construct (人工物) |
Chemical component information |
-実験情報
-構造解析
手法 | ネガティブ染色法, クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.6 mg/mL |
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緩衝液 | pH: 7.4 詳細: 20 mM Hepes pH7.4, 40 mM KCH3COO, 10 mM NH4CH3COO, 10 mM Mg(CH3COO)2 and 5 mM 2-mecaptoethanol |
染色 | タイプ: NEGATIVE / 詳細: cryo-EM |
グリッド | 詳細: 30 s on glow-discharged holey carbon grids (Quantifoil R2/2), onto which a home-made continuous carbon film |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 90 K / 装置: FEI VITROBOT MARK IV / 手法: Blot 2.5 seconds before plunging |
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電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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温度 | 最低: 80 K / 最高: 90 K / 平均: 85 K |
アライメント法 | Legacy - 非点収差: Objective lens astigmatism was corrected at 78,000 times magnification |
日付 | 2014年1月19日 |
撮影 | カテゴリ: CCD フィルム・検出器のモデル: FEI FALCON II (4k x 4k) デジタル化 - サンプリング間隔: 14 µm / 実像数: 1083 / 平均電子線量: 20 e/Å2 詳細: Use a newly developed statistical movie processing approach to compensate for beam-induced movement. |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 倍率(補正後): 104748 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2 mm / 最大 デフォーカス(公称値): 3.8 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 78000 |
試料ステージ | 試料ホルダーモデル: GATAN LIQUID NITROGEN |
実験機器 | ![]() モデル: Tecnai Polara / 画像提供: FEI Company |
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画像解析
詳細 | Use a newly developed statistical movie processing approach to compensate for beam-induced movement. |
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CTF補正 | 詳細: Each particle |
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.2 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: CTFFIND3, RELION 詳細: Use a newly developed statistical movie processing approach to compensate for beam-induced movement. 使用した粒子像数: 105247 |