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データを開く
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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of the human 39S mitoribosome with Tigecycline | |||||||||
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![]() | 39S mitoribosome / Tigecycline / antibiotic / RIBOSOME | |||||||||
機能・相同性 | ![]() negative regulation of mitochondrial translation / mitochondrial large ribosomal subunit assembly / protein lipoylation / Complex I biogenesis / negative regulation of ribosome biogenesis / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / positive regulation of mitochondrial translation / Respiratory electron transport / mitochondrial translational termination ...negative regulation of mitochondrial translation / mitochondrial large ribosomal subunit assembly / protein lipoylation / Complex I biogenesis / negative regulation of ribosome biogenesis / Mitochondrial Fatty Acid Beta-Oxidation / Protein lipoylation / positive regulation of mitochondrial translation / Respiratory electron transport / mitochondrial translational termination / mitochondrial translational elongation / translation release factor activity, codon nonspecific / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / translation release factor activity / mitochondrial [2Fe-2S] assembly complex / iron-sulfur cluster assembly complex / mitochondrial large ribosomal subunit / mitochondrial fission / mitochondrial large ribosomal subunit binding / peptidyl-tRNA hydrolase / mitochondrial ribosome / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エンドリボヌクレアーゼ / mitochondrial small ribosomal subunit / peptidyl-tRNA hydrolase activity / [2Fe-2S] cluster assembly / mitochondrial translation / iron-sulfur cluster assembly / acyl binding / acyl carrier activity / ribosomal large subunit binding / mitochondrial respiratory chain complex I assembly / mitochondrial electron transport, NADH to ubiquinone / proton motive force-driven mitochondrial ATP synthesis / respiratory chain complex I / anatomical structure morphogenesis / RNA processing / rescue of stalled ribosome / Mitochondrial protein degradation / cellular response to leukemia inhibitory factor / aerobic respiration / ribosomal large subunit biogenesis / fatty acid binding / mitochondrial membrane / fibrillar center / fatty acid biosynthetic process / cell junction / large ribosomal subunit / double-stranded RNA binding / large ribosomal subunit rRNA binding / small ribosomal subunit rRNA binding / endonuclease activity / mitochondrial inner membrane / negative regulation of translation / rRNA binding / nuclear body / ribosome / structural constituent of ribosome / mitochondrial matrix / protein domain specific binding / translation / ribonucleoprotein complex / nucleotide binding / mRNA binding / apoptotic process / calcium ion binding / nucleolus / mitochondrion / RNA binding / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm 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 / 解像度: 3.4 Å | |||||||||
![]() | Li X / Wang M / Cheng J | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis for differential inhibition of eukaryotic ribosomes by tigecycline. 著者: Xiang Li / Mengjiao Wang / Timo Denk / Robert Buschauer / Yi Li / Roland Beckmann / Jingdong Cheng / ![]() ![]() 要旨: Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, ...Tigecycline is widely used for treating complicated bacterial infections for which there are no effective drugs. It inhibits bacterial protein translation by blocking the ribosomal A-site. However, even though it is also cytotoxic for human cells, the molecular mechanism of its inhibition remains unclear. Here, we present cryo-EM structures of tigecycline-bound human mitochondrial 55S, 39S, cytoplasmic 80S and yeast cytoplasmic 80S ribosomes. We find that at clinically relevant concentrations, tigecycline effectively targets human 55S mitoribosomes, potentially, by hindering A-site tRNA accommodation and by blocking the peptidyl transfer center. In contrast, tigecycline does not bind to human 80S ribosomes under physiological concentrations. However, at high tigecycline concentrations, in addition to blocking the A-site, both human and yeast 80S ribosomes bind tigecycline at another conserved binding site restricting the movement of the L1 stalk. In conclusion, the observed distinct binding properties of tigecycline may guide new pathways for drug design and therapy. | |||||||||
履歴 |
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構造の表示
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 | ![]() | 225.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 72.1 KB 72.1 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 14.8 KB | 表示 | ![]() |
画像 | ![]() | 122.4 KB | ||
Filedesc metadata | ![]() | 15.2 KB | ||
その他 | ![]() ![]() | 226 MB 225.7 MB | ||
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 | ![]() 8k2bMC ![]() 8k2aC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 8yopC 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 | 類似検索 - 機能・相同性 ![]() |
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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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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.19 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: consensus map
ファイル | emd_36837_half_map_1.map | ||||||||||||
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注釈 | consensus map | ||||||||||||
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_36837_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 : 55S mitoribosome with tigecycline
+超分子 #1: 55S mitoribosome with tigecycline
+分子 #1: 16s rRNA
+分子 #2: Val tRNA
+分子 #3: Large ribosomal subunit protein uL2m
+分子 #4: Large ribosomal subunit protein uL3m
+分子 #5: Large ribosomal subunit protein uL4m
+分子 #6: Large ribosomal subunit protein bL9m
+分子 #7: Large ribosomal subunit protein uL10m
+分子 #8: Large ribosomal subunit protein uL11m
+分子 #9: Large ribosomal subunit protein uL13m
+分子 #10: Large ribosomal subunit protein uL14m
+分子 #11: Large ribosomal subunit protein uL15m
+分子 #12: Large ribosomal subunit protein uL16m
+分子 #13: Large ribosomal subunit protein bL17m
+分子 #14: Mitochondrial ribosomal protein L18, isoform CRA_b
+分子 #15: Large ribosomal subunit protein bL19m
+分子 #16: Large ribosomal subunit protein bL20m
+分子 #17: Large ribosomal subunit protein bL21m
+分子 #18: 39S ribosomal protein L22, mitochondrial
+分子 #19: Large ribosomal subunit protein uL23m
+分子 #20: Large ribosomal subunit protein uL24m
+分子 #21: Large ribosomal subunit protein bL27m
+分子 #22: Large ribosomal subunit protein bL28m
+分子 #23: Large ribosomal subunit protein uL29m
+分子 #24: Large ribosomal subunit protein uL30m
+分子 #25: Large ribosomal subunit protein bL32m
+分子 #26: Large ribosomal subunit protein bL33m
+分子 #27: Large ribosomal subunit protein bL34m
+分子 #28: Large ribosomal subunit protein bL35m
+分子 #29: Large ribosomal subunit protein bL36m
+分子 #30: Large ribosomal subunit protein mL37
+分子 #31: Large ribosomal subunit protein mL38
+分子 #32: Large ribosomal subunit protein mL39
+分子 #33: Large ribosomal subunit protein mL40
+分子 #34: Large ribosomal subunit protein mL41
+分子 #35: Large ribosomal subunit protein mL42
+分子 #36: Large ribosomal subunit protein mL43
+分子 #37: Large ribosomal subunit protein mL44
+分子 #38: Large ribosomal subunit protein mL45
+分子 #39: Large ribosomal subunit protein mL46
+分子 #40: Large ribosomal subunit protein mL48
+分子 #41: Large ribosomal subunit protein mL49
+分子 #42: Large ribosomal subunit protein mL50
+分子 #43: Large ribosomal subunit protein mL51
+分子 #44: 39S ribosomal protein L52, mitochondrial
+分子 #45: Large ribosomal subunit protein mL53
+分子 #46: Large ribosomal subunit protein mL54
+分子 #47: Large ribosomal subunit protein mL55
+分子 #48: Large ribosomal subunit protein mL63
+分子 #49: Large ribosomal subunit protein mL62
+分子 #50: Large ribosomal subunit protein mL64
+分子 #51: Large ribosomal subunit protein mL66
+分子 #52: Large ribosomal subunit protein mL65
+分子 #53: Mitochondrial assembly of ribosomal large subunit protein 1
+分子 #54: Mitochondrial ribosome and complex I assembly factor AltMIEF1
+分子 #55: Acyl carrier protein, mitochondrial
+分子 #56: MAGNESIUM ION
+分子 #57: TIGECYCLINE
+分子 #58: ZINC ION
+分子 #59: 4'-PHOSPHOPANTETHEINE
-実験情報
-構造解析
手法 | 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
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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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: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |