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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 80S ribosome with Tigecycline, e-tRNA and CCDC124 (40S head Swivelled) | |||||||||
マップデータ | refined map without post process | |||||||||
試料 |
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キーワード | ribosome / Tigecycline / antibiotic / CCDC124 | |||||||||
| 機能・相同性 | 機能・相同性情報ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV ...ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / embryonic brain development / translation at presynapse / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of formation of translation preinitiation complex / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / alpha-beta T cell differentiation / positive regulation of DNA-templated transcription initiation / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / protein kinase A binding / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / laminin receptor activity / Translation initiation complex formation / homeostatic process / pigmentation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / TOR signaling / positive regulation of GTPase activity / iron-sulfur cluster binding / mTORC1-mediated signalling / Peptide chain elongation / regulation of cell division / Selenocysteine synthesis / Formation of a pool of free 40S subunits / cellular response to ethanol / blastocyst development / Eukaryotic Translation Termination / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / SRP-dependent cotranslational protein targeting to membrane / Response of EIF2AK4 (GCN2) to amino acid deficiency / negative regulation of protein binding / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / ubiquitin ligase inhibitor activity / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of signal transduction by p53 class mediator / GTP hydrolysis and joining of the 60S ribosomal subunit / protein localization to nucleus / negative regulation of ubiquitin-dependent protein catabolic process 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | |||||||||
データ登録者 | Li X / Wang M / 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. | |||||||||
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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 | emd_38630.map.gz | 338.7 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-38630-v30.xml emd-38630.xml | 109.8 KB 109.8 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_38630_fsc.xml | 17 KB | 表示 | FSCデータファイル |
| 画像 | emd_38630.png | 116.7 KB | ||
| Filedesc metadata | emd-38630.cif.gz | 21.1 KB | ||
| その他 | emd_38630_additional_1.map.gz emd_38630_half_map_1.map.gz emd_38630_half_map_2.map.gz | 241.7 MB 338.6 MB 338.7 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-38630 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38630 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 8xsyMC ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 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 F&H 検索 |
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_38630.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 | refined map without post process | ||||||||||||||||||||||||||||||||||||
| 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: 0.932 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: local resolution filtered map using Relion
| ファイル | emd_38630_additional_1.map | ||||||||||||
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| 注釈 | local resolution filtered map using Relion | ||||||||||||
| 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_38630_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: #1
| ファイル | emd_38630_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 : 80S ribosome with tigecycline, E-tRNA and CCDC124
+超分子 #1: 80S ribosome with tigecycline, E-tRNA and CCDC124
+分子 #1: 28S rRNA
+分子 #2: 5S rRNA
+分子 #3: 5.8S rRNA
+分子 #49: 18S rRNA
+分子 #85: E-tRNA
+分子 #4: 60S ribosomal protein L8
+分子 #5: 60S ribosomal protein L3
+分子 #6: 60S ribosomal protein L4
+分子 #7: 60S ribosomal protein L5
+分子 #8: 60S ribosomal protein L6
+分子 #9: 60S ribosomal protein L7
+分子 #10: 60S ribosomal protein L7a
+分子 #11: 60S ribosomal protein L9
+分子 #12: Large ribosomal subunit protein uL16
+分子 #13: 60S ribosomal protein L11
+分子 #14: 60S ribosomal protein L13
+分子 #15: 60S ribosomal protein L14
+分子 #16: 60S ribosomal protein L15
+分子 #17: 60S ribosomal protein L13a
+分子 #18: 60S ribosomal protein L17
+分子 #19: 60S ribosomal protein L18
+分子 #20: 60S ribosomal protein L19
+分子 #21: 60S ribosomal protein L18a
+分子 #22: 60S ribosomal protein L21
+分子 #23: 60S ribosomal protein L22
+分子 #24: 60S ribosomal protein L23
+分子 #25: 60S ribosomal protein L24
+分子 #26: 60S ribosomal protein L23a
+分子 #27: 60S ribosomal protein L26
+分子 #28: 60S ribosomal protein L27
+分子 #29: 60S ribosomal protein L27a
+分子 #30: 60S ribosomal protein L29
+分子 #31: 60S ribosomal protein L30
+分子 #32: 60S ribosomal protein L31
+分子 #33: 60S ribosomal protein L32
+分子 #34: 60S ribosomal protein L35a
+分子 #35: 60S ribosomal protein L34
+分子 #36: 60S ribosomal protein L35
+分子 #37: 60S ribosomal protein L36
+分子 #38: 60S ribosomal protein L37
+分子 #39: 60S ribosomal protein L38
+分子 #40: 60S ribosomal protein L39
+分子 #41: Ubiquitin-60S ribosomal protein L40
+分子 #42: 60S ribosomal protein L41
+分子 #43: 60S ribosomal protein L36a
+分子 #44: 60S ribosomal protein L37a
+分子 #45: 60S ribosomal protein L28
+分子 #46: Large ribosomal subunit protein uL10
+分子 #47: 60S ribosomal protein L12
+分子 #48: 60S ribosomal protein L10a
+分子 #50: 40S ribosomal protein SA
+分子 #51: 40S ribosomal protein S3a
+分子 #52: 40S ribosomal protein S3
+分子 #53: 40S ribosomal protein S4, X isoform
+分子 #54: 40S ribosomal protein S5
+分子 #55: 40S ribosomal protein S7
+分子 #56: 40S ribosomal protein S8
+分子 #57: 40S ribosomal protein S10
+分子 #58: 40S ribosomal protein S11
+分子 #59: 40S ribosomal protein S15
+分子 #60: 40S ribosomal protein S16
+分子 #61: 40S ribosomal protein S17
+分子 #62: 40S ribosomal protein S18
+分子 #63: 40S ribosomal protein S19
+分子 #64: 40S ribosomal protein S20
+分子 #65: 40S ribosomal protein S21
+分子 #66: 40S ribosomal protein S23
+分子 #67: 40S ribosomal protein S26
+分子 #68: 40S ribosomal protein S28
+分子 #69: 40S ribosomal protein S29
+分子 #70: Receptor of activated protein C kinase 1
+分子 #71: 40S ribosomal protein S2
+分子 #72: 40S ribosomal protein S6
+分子 #73: 40S ribosomal protein S9
+分子 #74: 40S ribosomal protein S12
+分子 #75: 40S ribosomal protein S13
+分子 #76: 40S ribosomal protein S14
+分子 #77: 40S ribosomal protein S15a
+分子 #78: 40S ribosomal protein S24
+分子 #79: 40S ribosomal protein S25
+分子 #80: 40S ribosomal protein S27
+分子 #81: 40S ribosomal protein S30
+分子 #82: Ubiquitin-40S ribosomal protein S27a
+分子 #83: Proliferation-associated protein 2G4
+分子 #84: SERPINE1 mRNA-binding protein 1
+分子 #86: Coiled-coil domain-containing protein 124
+分子 #87: MAGNESIUM ION
+分子 #88: TIGECYCLINE
+分子 #89: 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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解析 | 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 / 前処理 - タイプ: GLOW DISCHARGE |
| 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: 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): 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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コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
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Z (Sec.)
Y (Row.)
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解析
FIELD EMISSION GUN


