+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-11951 | |||||||||
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タイトル | Context-specific inhibition of eukaryotic translation by macrolide antibiotics | |||||||||
マップデータ | Focused refinement for reconstruction of S. cervisiea ribosome with telithromycin at a final resolution of 2.9 A | |||||||||
試料 |
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キーワード | context-specific inhibition / macrolide antibiotic / ribosome / telithromycin | |||||||||
機能・相同性 | 機能・相同性情報 cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / 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) / L13a-mediated translational silencing of Ceruloplasmin expression / preribosome, large subunit precursor / ribosomal large subunit export from nucleus ...cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / 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) / L13a-mediated translational silencing of Ceruloplasmin expression / preribosome, large subunit precursor / ribosomal large subunit export from nucleus / regulation of translational fidelity / protein-RNA complex assembly / translational termination / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA / ribosomal large subunit biogenesis / macroautophagy / maintenance of translational fidelity / ribosomal large subunit assembly / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosome biogenesis / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / protein ubiquitination / structural constituent of ribosome / translation / response to antibiotic / mRNA binding / ubiquitin protein ligase binding / RNA binding / nucleus / metal ion binding / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (パン酵母) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.877 Å | |||||||||
データ登録者 | Koller TO / Wilson DN | |||||||||
資金援助 | ドイツ, 1件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Context-specific action of macrolide antibiotics on the eukaryotic ribosome. 著者: Maxim S Svetlov / Timm O Koller / Sezen Meydan / Vaishnavi Shankar / Dorota Klepacki / Norbert Polacek / Nicholas R Guydosh / Nora Vázquez-Laslop / Daniel N Wilson / Alexander S Mankin / 要旨: Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of ...Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells. | |||||||||
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_11951.map.gz | 265.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-11951-v30.xml emd-11951.xml | 61.9 KB 61.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_11951_fsc.xml | 14.9 KB | 表示 | FSCデータファイル |
画像 | emd_11951.png | 44.4 KB | ||
Filedesc metadata | emd-11951.cif.gz | 13.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-11951 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11951 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_11951_validation.pdf.gz | 736.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_11951_full_validation.pdf.gz | 736.2 KB | 表示 | |
XML形式データ | emd_11951_validation.xml.gz | 14.5 KB | 表示 | |
CIF形式データ | emd_11951_validation.cif.gz | 19.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11951 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11951 | 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_11951.map.gz / 形式: CCP4 / 大きさ: 282.6 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Focused refinement for reconstruction of S. cervisiea ribosome with telithromycin at a final resolution of 2.9 A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.822 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 : 60S ribosomal subunit with 25S rRNA mutation G2400A and telithrom...
+超分子 #1: 60S ribosomal subunit with 25S rRNA mutation G2400A and telithrom...
+分子 #1: 60S ribosomal protein L8-A
+分子 #2: 60S ribosomal protein L23-A
+分子 #3: 60S ribosomal protein L36-A
+分子 #4: 60S ribosomal protein L9-A
+分子 #5: 60S ribosomal protein L24-A
+分子 #6: 60S ribosomal protein L37-A
+分子 #7: 60S ribosomal protein L11-B
+分子 #8: 60S ribosomal protein L25
+分子 #9: 60S ribosomal protein L38
+分子 #10: 60S ribosomal protein L13-A
+分子 #11: 60S ribosomal protein L26-A
+分子 #12: 60S ribosomal protein L39
+分子 #13: 60S ribosomal protein L14-A
+分子 #14: 60S ribosomal protein L27-A
+分子 #15: Ubiquitin-60S ribosomal protein L40
+分子 #16: 60S ribosomal protein L42-A
+分子 #17: 60S ribosomal protein L15-A
+分子 #18: 60S ribosomal protein L28
+分子 #19: 60S ribosomal protein L43-A
+分子 #20: 60S ribosomal protein L16-A
+分子 #21: 60S ribosomal protein L29
+分子 #22: 60S ribosomal protein L2-A
+分子 #23: 60S ribosomal protein L17-A
+分子 #24: 60S ribosomal protein L3
+分子 #25: 60S ribosomal protein L18-A
+分子 #26: 60S ribosomal protein L31-A
+分子 #27: 60S ribosomal protein L10
+分子 #28: 60S ribosomal protein L4-A
+分子 #29: 60S ribosomal protein L32
+分子 #30: 60S ribosomal protein L20-A
+分子 #31: 60S ribosomal protein L5
+分子 #32: 60S ribosomal protein L21-A
+分子 #33: 60S ribosomal protein L33-A
+分子 #34: 60S ribosomal protein L22-A
+分子 #35: 60S ribosomal protein L6-A
+分子 #36: 60S ribosomal protein L34-A
+分子 #37: 60S ribosomal protein L7-A
+分子 #38: 60S ribosomal protein L35-A
+分子 #42: 60S ribosomal protein L19-A
+分子 #39: 25S ribosomal RNA
+分子 #40: 5S ribosomal RNA
+分子 #41: 5.8S ribosomal RNA
+分子 #43: TELITHROMYCIN
+分子 #44: water
-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 構成要素:
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グリッド | モデル: Quantifoil R3/3 / 材質: COPPER / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 支持フィルム - Film thickness: 3 / 前処理 - タイプ: PLASMA CLEANING | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK III | ||||||||||||||||||
詳細 | 5 Optical density at 260 nm. Approximatly 100 pmol of ribosome complex per grid. |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 撮影したグリッド数: 1 / 実像数: 4371 / 平均電子線量: 30.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |