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- EMDB-38635: Cryo-EM structure of the human 39S mitoribosome with 10uM Tigecycline -
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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 10uM Tigecycline | |||||||||
![]() | refined map without post process | |||||||||
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![]() | ribosome / Tigecycline / antibiotic / CCDC124 | |||||||||
機能・相同性 | ![]() mitochondrial translational elongation / mitochondrial translational termination / translation release factor activity, codon nonspecific / microprocessor complex / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / 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 large ribosomal subunit / peptidyl-tRNA hydrolase ...mitochondrial translational elongation / mitochondrial translational termination / translation release factor activity, codon nonspecific / microprocessor complex / Mitochondrial translation elongation / Mitochondrial translation termination / Mitochondrial translation initiation / 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 large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial small ribosomal subunit / aminoacyl-tRNA hydrolase activity / mitochondrial ribosome / mitochondrial translation / anatomical structure morphogenesis / RNA processing / Mitochondrial protein degradation / rescue of stalled ribosome / cellular response to leukemia inhibitory factor / fibrillar center / double-stranded RNA binding / cell junction / small ribosomal subunit rRNA binding / 5S rRNA binding / large ribosomal subunit rRNA binding / endonuclease activity / cytosolic large ribosomal subunit / mitochondrial inner membrane / cytoplasmic translation / nuclear body / rRNA binding / negative regulation of translation / ribosome / structural constituent of ribosome / mitochondrial matrix / ribonucleoprotein complex / translation / cell cycle / protein domain specific binding / nucleotide binding / mRNA binding / apoptotic process / synapse / nucleolus / mitochondrion / RNA binding / nucleoplasm / nucleus / plasma membrane / 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 / 解像度: 3.1 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
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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 | ![]() | |||
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ヘッダ (付随情報) | ![]() | |||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1 MB | 表示 | |
XML形式データ | ![]() | 22.7 KB | 表示 | |
CIF形式データ | ![]() | 30 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 | ![]() 8xt3MC ![]() 36836 ![]() 36837 ![]() 36838 ![]() 36839 ![]() 36945 ![]() 38629 ![]() 38630 ![]() 38631 ![]() 38632 ![]() 38633 ![]() 38634 ![]() 38636 ![]() 38637 ![]() 38638 ![]() 38639 ![]() 39455 ![]() 39456 ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 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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注釈 | refined map without post process | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.064 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
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試料の構成要素
+全体 : 55S ribosome with tigecycline
+超分子 #1: 55S ribosome 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: MAGNESIUM ION
+分子 #54: TIGECYCLINE
+分子 #55: ZINC ION
-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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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: CONTINUOUS / 支持フィルム - Film thickness: 2 |
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: GATAN K3 (6k 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 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: OTHER / 詳細: Relion |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION / 使用した粒子像数: 52961 |
初期 角度割当 | タイプ: OTHER / ソフトウェア - 名称: RELION / 詳細: Relion |
最終 角度割当 | タイプ: OTHER / ソフトウェア - 名称: RELION / 詳細: Relion |