+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-6454 | |||||||||
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タイトル | Cryo-electron microscopy reconstruction of the P. falciparum 80S ribosome bound to E-tRNA | |||||||||
マップデータ | Cryo-EM reconstruction of the P. falciparum schizont-stage ribosome in a non-rotated state, bound to E-tRNA | |||||||||
試料 |
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キーワード | Cryo-EM (低温電子顕微鏡法) / malaria (マラリア) / translational pausing / RACK1 | |||||||||
機能・相同性 | 機能・相同性情報 RMTs methylate histone arginines / Protein methylation / Translesion synthesis by REV1 / Translesion Synthesis by POLH / : / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / : / Metalloprotease DUBs ...RMTs methylate histone arginines / Protein methylation / Translesion synthesis by REV1 / Translesion Synthesis by POLH / : / Translesion synthesis by POLK / Translesion synthesis by POLI / Josephin domain DUBs / : / Metalloprotease DUBs / 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 / Major pathway of rRNA processing in the nucleolus and cytosol / 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 / 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 / KEAP1-NFE2L2 pathway / UCH proteinases / Ub-specific processing proteases / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / 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 SSU-rRNA / maturation of SSU-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) / maturation of LSU-rRNA / ribosomal large subunit biogenesis / small-subunit processome / modification-dependent protein catabolic process / mRNA 5'-UTR binding / ribosomal small subunit biogenesis / ribosomal large subunit assembly / small ribosomal subunit rRNA binding / protein tag activity / ribosomal small subunit assembly / rRNA processing / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / large ribosomal subunit / リボソーム生合成 / cytoplasmic translation / small ribosomal subunit / 5S rRNA binding / cytosolic large ribosomal subunit / ubiquitin-dependent protein catabolic process / negative regulation of translation / rRNA binding / protein ubiquitination / リボソーム / structural constituent of ribosome / ribonucleoprotein complex / 翻訳 (生物学) / mRNA binding / ubiquitin protein ligase binding / 核小体 / ミトコンドリア / RNA binding / zinc ion binding / metal ion binding / 細胞核 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Plasmodium falciparum (マラリア病原虫) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.7 Å | |||||||||
データ登録者 | Sun M / Li W / Blomqvist K / Das S / Hashem Y / Dvorin JD / Frank J | |||||||||
引用 | ジャーナル: Elife / 年: 2014 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 |
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_6454.map.gz | 23.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-6454-v30.xml emd-6454.xml | 10.9 KB 10.9 KB | 表示 表示 | EMDBヘッダ |
画像 | 400_6454.gif 80_6454.gif | 61.8 KB 4.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-6454 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6454 | 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_6454.map.gz / 形式: CCP4 / 大きさ: 96.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Cryo-EM reconstruction of the P. falciparum schizont-stage ribosome in a non-rotated state, bound to E-tRNA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.66 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
-試料の構成要素
-全体 : The schizont-stage Plasmodium falciparum 80S ribosome bound to E-tRNA
全体 | 名称: The schizont-stage Plasmodium falciparum 80S ribosome bound to E-tRNA |
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要素 |
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-超分子 #1000: The schizont-stage Plasmodium falciparum 80S ribosome bound to E-tRNA
超分子 | 名称: The schizont-stage Plasmodium falciparum 80S ribosome bound to E-tRNA タイプ: sample / ID: 1000 / Number unique components: 1 |
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-超分子 #1: 80S ribosome
超分子 | 名称: 80S ribosome / タイプ: complex / ID: 1 / 組換発現: No / データベース: NCBI / Ribosome-details: ribosome-eukaryote: ALL |
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由来(天然) | 生物種: Plasmodium falciparum (マラリア病原虫) / 株: 3D7 / 別称: Plasmodium |
-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: 7.5 詳細: 10 mM HEPES potassium, 50 mM KOAc, 10 mM NH4Cl, 2 mM DTT, 5 mM Mg(OAc)2 |
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グリッド | 詳細: 300 mesh Copper/Molbydenum holey carton-coated Quantifoil R2/4 grid, containing an additional continuous thin layer of carbon |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / 装置: FEI VITROBOT MARK IV / 手法: Blot for 4 seconds before plunging. |
-電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 倍率(補正後): 30120 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 2.26 mm / 最大 デフォーカス(公称値): 3.5 µm / 最小 デフォーカス(公称値): 1.5 µm / 倍率(公称値): 23000 |
試料ステージ | 試料ホルダーモデル: GATAN HELIUM |
日付 | 2013年10月13日 |
撮影 | カテゴリ: CCD / フィルム・検出器のモデル: GATAN K2 (4k x 4k) / 実像数: 5734 / 平均電子線量: 25 e/Å2 |
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
-画像解析
CTF補正 | 詳細: Each micrograph |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.7 Å / 解像度の算出法: OTHER / ソフトウェア - 名称: Arachnid, CTFFIND3, RELION / 使用した粒子像数: 96732 |
詳細 | See 'Materials and Methods' in Sun, M., et al 2015 |
-原子モデル構築 1
初期モデル | PDB ID: |
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ソフトウェア | 名称: MDFF |
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
得られたモデル | PDB-3jbp: |