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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 yeast 80S ribosome with tigecycline, eEF2, Stm1 and eIF5A | |||||||||
![]() | DeepEMhancer | |||||||||
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![]() | 80S ribosome / tigecycline / antibiotic / RIBOSOME | |||||||||
機能・相同性 | ![]() positive regulation of cytoplasmic translational elongation through polyproline stretches / Hypusine synthesis from eIF5A-lysine / CAT tailing / translational frameshifting / Peptide chain elongation / Synthesis of diphthamide-EEF2 / positive regulation of translational termination / triplex DNA binding / ribosome hibernation / translation elongation factor binding ...positive regulation of cytoplasmic translational elongation through polyproline stretches / Hypusine synthesis from eIF5A-lysine / CAT tailing / translational frameshifting / Peptide chain elongation / Synthesis of diphthamide-EEF2 / positive regulation of translational termination / triplex DNA binding / ribosome hibernation / translation elongation factor binding / regulation of translational initiation in response to stress / Platelet degranulation / positive regulation of translational elongation / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, LSU-rRNA,5S) / negative regulation of glucose mediated signaling pathway / negative regulation of translational frameshifting / Negative regulators of DDX58/IFIH1 signaling / positive regulation of translational fidelity / Protein methylation / RMTs methylate histone arginines / mTORC1-mediated signalling / Protein hydroxylation / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay / pre-mRNA 5'-splice site binding / Formation of the ternary complex, and subsequently, the 43S complex / Translation initiation complex formation / Ribosomal scanning and start codon recognition / translational elongation / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / preribosome, small subunit precursor / response to cycloheximide / telomeric DNA binding / mRNA destabilization / Major pathway of rRNA processing in the nucleolus and cytosol / 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) / negative regulation of mRNA splicing, via spliceosome / L13a-mediated translational silencing of Ceruloplasmin expression / preribosome, large subunit precursor / ribosomal large subunit export from nucleus / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / G-protein alpha-subunit binding / TOR signaling / positive regulation of protein kinase activity / protein-RNA complex assembly / positive regulation of translational initiation / regulation of translational fidelity / Ub-specific processing proteases / ribosomal small subunit export from nucleus / translation regulator activity / translation elongation factor activity / ribosomal subunit export from nucleus / translational termination / 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) / translation repressor activity / DNA-(apurinic or apyrimidinic site) endonuclease activity / Neutrophil degranulation / translation initiation factor activity / cellular response to amino acid starvation / ribosome assembly / telomere maintenance / rescue of stalled ribosome / 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 / macroautophagy / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / maintenance of translational fidelity / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / ribosomal large subunit assembly / cytoplasmic stress granule / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosome biogenesis / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / protein-folding chaperone binding / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / negative regulation of translation / ribosome / protein ubiquitination 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: 3.2 Å | |||||||||
![]() | Buschauer R / Beckmann R / 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 | ![]() | 928.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 927.9 KB | 表示 | |
XML形式データ | ![]() | 25.1 KB | 表示 | |
CIF形式データ | ![]() | 33.1 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 | ![]() 8k2dMC ![]() 36836 ![]() 36837 ![]() 36838 ![]() 36945 ![]() 38629 ![]() 38630 ![]() 38631 ![]() 38632 ![]() 38633 ![]() 38634 ![]() 38635 ![]() 38636 ![]() 38637 ![]() 38638 ![]() 38639 ![]() 39455 ![]() 39456 ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 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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注釈 | DeepEMhancer | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.847 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 : yeast 80S ribosome
+超分子 #1: yeast 80S ribosome
+分子 #1: 18S rRNA
+分子 #2: 23S rRNA
+分子 #3: 5S rRNA
+分子 #4: 5.8S rRNA
+分子 #5: Small ribosomal subunit protein uS2A
+分子 #6: 40S ribosomal protein S1-A
+分子 #7: 40S ribosomal protein S2
+分子 #8: Small ribosomal subunit protein uS3
+分子 #9: 40S ribosomal protein S4-A
+分子 #10: Small ribosomal subunit protein uS7
+分子 #11: 40S ribosomal protein S6-A
+分子 #12: 40S ribosomal protein S7-A
+分子 #13: 40S ribosomal protein S8-A
+分子 #14: 40S ribosomal protein S9-A
+分子 #15: Small ribosomal subunit protein eS10A
+分子 #16: Small ribosomal subunit protein uS17A
+分子 #17: Small ribosomal subunit protein eS12
+分子 #18: 40S ribosomal protein S13
+分子 #19: 40S ribosomal protein S14-A
+分子 #20: Small ribosomal subunit protein uS19
+分子 #21: Small ribosomal subunit protein uS9A
+分子 #22: Small ribosomal subunit protein eS17A
+分子 #23: Small ribosomal subunit protein uS13A
+分子 #24: Small ribosomal subunit protein eS19A
+分子 #25: Small ribosomal subunit protein uS10
+分子 #26: Small ribosomal subunit protein eS21A
+分子 #27: 40S ribosomal protein S22-A
+分子 #28: 40S ribosomal protein S23-A
+分子 #29: 40S ribosomal protein S24-A
+分子 #30: Small ribosomal subunit protein eS25A
+分子 #31: Small ribosomal subunit protein eS26B
+分子 #32: 40S ribosomal protein S27-A
+分子 #33: Small ribosomal subunit protein eS28A
+分子 #34: Small ribosomal subunit protein uS14A
+分子 #35: 40S ribosomal protein S30-A
+分子 #36: Ubiquitin-ribosomal protein eS31 fusion protein
+分子 #37: Small ribosomal subunit protein RACK1
+分子 #38: Large ribosomal subunit protein uL2A
+分子 #39: Large ribosomal subunit protein uL3
+分子 #40: Large ribosomal subunit protein uL4A
+分子 #41: Large ribosomal subunit protein uL18
+分子 #42: Large ribosomal subunit protein eL6A
+分子 #43: Large ribosomal subunit protein uL30A
+分子 #44: Large ribosomal subunit protein eL8A
+分子 #45: Large ribosomal subunit protein uL6A
+分子 #46: Large ribosomal subunit protein uL16
+分子 #47: Large ribosomal subunit protein uL5A
+分子 #48: Large ribosomal subunit protein uL11A
+分子 #49: Large ribosomal subunit protein eL13A
+分子 #50: Large ribosomal subunit protein eL14A
+分子 #51: Large ribosomal subunit protein eL15A
+分子 #52: Large ribosomal subunit protein uL13A
+分子 #53: Large ribosomal subunit protein uL22A
+分子 #54: Large ribosomal subunit protein eL18A
+分子 #55: Large ribosomal subunit protein eL19A
+分子 #56: Large ribosomal subunit protein eL20A
+分子 #57: Large ribosomal subunit protein eL21A
+分子 #58: Large ribosomal subunit protein eL22A
+分子 #59: Large ribosomal subunit protein uL14A
+分子 #60: Large ribosomal subunit protein eL24A
+分子 #61: Large ribosomal subunit protein uL23
+分子 #62: Large ribosomal subunit protein uL24A
+分子 #63: Large ribosomal subunit protein eL27A
+分子 #64: Large ribosomal subunit protein uL15
+分子 #65: Large ribosomal subunit protein eL29
+分子 #66: Large ribosomal subunit protein eL30
+分子 #67: Large ribosomal subunit protein eL31A
+分子 #68: Large ribosomal subunit protein eL32
+分子 #69: Large ribosomal subunit protein eL33A
+分子 #70: Large ribosomal subunit protein eL34A
+分子 #71: Large ribosomal subunit protein uL29A
+分子 #72: Large ribosomal subunit protein eL36A
+分子 #73: Large ribosomal subunit protein eL37A
+分子 #74: Large ribosomal subunit protein eL38
+分子 #75: Large ribosomal subunit protein eL39
+分子 #76: Ubiquitin-ribosomal protein eL40A fusion protein
+分子 #77: Large ribosomal subunit protein eL41A
+分子 #78: Large ribosomal subunit protein eL42A
+分子 #79: Large ribosomal subunit protein eL43A
+分子 #80: Eukaryotic translation initiation factor 5A-1
+分子 #81: Large ribosomal subunit protein uL1A
+分子 #82: Large ribosomal subunit protein uL10
+分子 #83: Elongation factor 2
+分子 #84: Suppressor protein STM1
+分子 #85: ZINC ION
+分子 #86: TIGECYCLINE
+分子 #87: MAGNESIUM ION
+分子 #88: GUANOSINE-5'-DIPHOSPHATE
-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: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 44.0 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): 3.5 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 |
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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: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 105095 |
初期 角度割当 | タイプ: OTHER / 詳細: Relion |
最終 角度割当 | タイプ: OTHER / 詳細: Relion |