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基本情報
登録情報 | データベース: PDB / ID: 8xsx | ||||||
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タイトル | Cryo-EM structure of the human 80S ribosome with Tigecycline, E-tRNA, SERBP1 and eEF2 | ||||||
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![]() | RIBOSOME / Tigecycline / antibiotic / eEF2 / SERBP1 | ||||||
機能・相同性 | ![]() Synthesis of diphthamide-EEF2 / translation at postsynapse / ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / response to folic acid / translation at presynapse / exit from mitosis / male meiosis I ...Synthesis of diphthamide-EEF2 / translation at postsynapse / ribosome hibernation / translation elongation factor binding / PML body organization / SUMO binding / response to folic acid / translation at presynapse / exit from mitosis / male meiosis I / eukaryotic 80S initiation complex / negative regulation of protein neddylation / optic nerve development / response to insecticide / negative regulation of endoplasmic reticulum unfolded protein response / regulation of translation involved in cellular response to UV / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / ribosomal protein import into nucleus / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of cytoplasmic translation / positive regulation of gastrulation / 90S preribosome assembly / protein tyrosine kinase inhibitor activity / protein-DNA complex disassembly / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of Golgi to plasma membrane protein transport / retinal ganglion cell axon guidance / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / supercoiled DNA binding / TORC2 complex binding / alpha-beta T cell differentiation / neural crest cell differentiation / G1 to G0 transition / NF-kappaB complex / positive regulation of ubiquitin-protein transferase activity / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / aggresome / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / ubiquitin-like protein conjugating enzyme binding / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / middle ear morphogenesis / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / ion channel inhibitor activity / pigmentation / Ribosomal scanning and start codon recognition / homeostatic process / lncRNA binding / Translation initiation complex formation / positive regulation of mitochondrial depolarization / Uptake and function of diphtheria toxin / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / lung morphogenesis / monocyte chemotaxis / positive regulation of activated T cell proliferation / positive regulation of natural killer cell proliferation / negative regulation of translational frameshifting / Protein hydroxylation / TOR signaling / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / regulation of cell division / mTORC1-mediated signalling / cellular response to ethanol / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / iron-sulfur cluster binding / Peptide chain elongation / skeletal muscle cell differentiation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / blastocyst development / positive regulation of GTPase activity 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.4 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. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 5 MB | 表示 | ![]() |
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PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 2.5 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.5 MB | 表示 | |
XML形式データ | ![]() | 379.7 KB | 表示 | |
CIF形式データ | ![]() | 668.3 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 | ![]() 38629MC ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 8yooC ![]() 8yopC M: このデータのモデリングに利用したマップデータ 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
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集合体
登録構造単位 | ![]()
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要素
-RNA鎖 , 5種, 5分子 L5L7L8S2CC
#1: RNA鎖 | 分子量: 1640182.000 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#2: RNA鎖 | 分子量: 38998.078 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#3: RNA鎖 | 分子量: 50449.812 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#49: RNA鎖 | 分子量: 602776.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#85: RNA鎖 | 分子量: 24231.510 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+60S ribosomal protein ... , 43種, 43分子 LALBLCLDLELFLGLHLILJLKLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLd...
-タンパク質 , 7種, 7分子 LmLsSgSfCACBCD
#42: タンパク質 | 分子量: 14758.394 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#47: タンパク質 | 分子量: 34309.418 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#70: タンパク質 | 分子量: 35115.652 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#82: タンパク質 | 分子量: 18004.041 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#83: タンパク質 | 分子量: 43851.879 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#84: タンパク質 | 分子量: 95463.211 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() 参照: UniProt: P13639, 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 |
#86: タンパク質 | 分子量: 44341.781 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+40S ribosomal protein ... , 31種, 31分子 SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-非ポリマー , 4種, 275分子 






#87: 化合物 | ChemComp-MG / #88: 化合物 | ChemComp-T1C / #89: 化合物 | ChemComp-ZN / #90: 化合物 | ChemComp-ADP / | |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: 80S ribosome with tigecycline, E-tRNA, eEF2 and SERBP1 タイプ: RIBOSOME / Entity ID: #1-#86 / 由来: NATURAL |
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由来(天然) | 生物種: ![]() |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm |
試料ホルダ | 凍結剤: NITROGEN |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
EMソフトウェア |
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CTF補正 | 詳細: Relion / タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||||||||
3次元再構成 | 解像度: 2.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 88213 / 対称性のタイプ: POINT | |||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL | |||||||||||||||||||||
原子モデル構築 | PDB-ID: 6Z6M Accession code: 6Z6M / Source name: PDB / タイプ: experimental model |