+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36839 | |||||||||
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タイトル | Cryo-EM structure of the yeast 80S ribosome with tigecycline, eEF2, Stm1 and eIF5A | |||||||||
マップデータ | DeepEMhancer | |||||||||
試料 |
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キーワード | 80S ribosome / tigecycline / antibiotic / RIBOSOME | |||||||||
機能・相同性 | 機能・相同性情報 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 / Platelet degranulation / regulation of translational initiation in response to stress / 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 / Protein methylation / positive regulation of translational fidelity / RMTs methylate histone arginines / mTORC1-mediated signalling / Protein hydroxylation / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / nonfunctional rRNA decay / 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 / preribosome, small subunit precursor / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Ribosomal scanning and start codon recognition / 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 / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Formation of a pool of free 40S subunits / negative regulation of mRNA splicing, via spliceosome / regulation of amino acid metabolic process / preribosome, large subunit precursor / L13a-mediated translational silencing of Ceruloplasmin expression / translational elongation / ribosomal large subunit export from nucleus / G-protein alpha-subunit binding / TOR signaling / positive regulation of protein kinase activity / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / Ub-specific processing proteases / regulation of translational fidelity / protein-RNA complex assembly / positive regulation of translational initiation / translation elongation factor activity / ribosomal subunit export from nucleus / ribosomal small subunit export from nucleus / translation regulator activity / translational termination / translation repressor activity / 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) / Neutrophil degranulation / DNA-(apurinic or apyrimidinic site) endonuclease activity / translation initiation factor activity / maturation of LSU-rRNA / telomere maintenance / cellular response to amino acid starvation / rescue of stalled ribosome / ribosome assembly / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / translational initiation / macroautophagy / protein kinase C binding / maintenance of translational fidelity / cytoplasmic stress granule / modification-dependent protein catabolic process / rRNA processing / protein tag activity / 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 small subunit biogenesis / ribosome biogenesis / small ribosomal subunit rRNA binding / ribosome binding / ribosomal large subunit assembly / ribosomal small subunit assembly / protein-folding chaperone binding / small ribosomal subunit / large ribosomal subunit rRNA binding / 5S rRNA binding / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / cytoplasmic translation / negative regulation of translation / rRNA binding 類似検索 - 分子機能 | |||||||||
生物種 | Saccharomyces cerevisiae (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: 3.2 Å | |||||||||
データ登録者 | Buschauer R / Beckmann R / Cheng J | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Nat Commun / 年: 2024 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 | emd_36839.map.gz | 372.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36839-v30.xml emd-36839.xml | 107.8 KB 107.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_36839_fsc.xml | 17.1 KB | 表示 | FSCデータファイル |
画像 | emd_36839.png | 116.8 KB | ||
Filedesc metadata | emd-36839.cif.gz | 19.7 KB | ||
その他 | emd_36839_additional_1.map.gz emd_36839_additional_2.map.gz emd_36839_half_map_1.map.gz emd_36839_half_map_2.map.gz | 336.8 MB 244.4 MB 337.8 MB 338.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36839 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36839 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_36839_validation.pdf.gz | 928.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_36839_full_validation.pdf.gz | 927.9 KB | 表示 | |
XML形式データ | emd_36839_validation.xml.gz | 25.1 KB | 表示 | |
CIF形式データ | emd_36839_validation.cif.gz | 33.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36839 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36839 | HTTPS FTP |
-関連構造データ
関連構造データ | 8k2dMC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_36839.map.gz / 形式: CCP4 / 大きさ: 421.9 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | DeepEMhancer | ||||||||||||||||||||||||||||||||||||
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: 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
-追加マップ: consensus map
ファイル | emd_36839_additional_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 |
-追加マップ: local filter
ファイル | emd_36839_additional_2.map | ||||||||||||
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注釈 | local filter | ||||||||||||
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_36839_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_36839_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 |
-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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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: 7.4 |
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凍結 | 凍結剤: ETHANE |
-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: FIELD EMISSION GUN |
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 |