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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8yoo | ||||||
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タイトル | Cryo-EM structure of the human 80S ribosome with 100 um Tigecycline | ||||||
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![]() | RIBOSOME / Tigecycline / antibiotic / eEF2 / SERBP1 | ||||||
機能・相同性 | ![]() translation at presynapse / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / optic nerve development / negative regulation of endoplasmic reticulum unfolded protein response / regulation of G1 to G0 transition / axial mesoderm development ...translation at presynapse / embryonic brain development / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / optic nerve development / negative regulation of endoplasmic reticulum unfolded protein response / regulation of G1 to G0 transition / axial mesoderm development / oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of formation of translation preinitiation complex / positive regulation of base-excision repair / regulation of translation involved in cellular response to UV / 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 / protein-DNA complex disassembly / positive regulation of gastrulation / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 90S preribosome assembly / protein tyrosine kinase inhibitor activity / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / retinal ganglion cell axon guidance / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / supercoiled DNA binding / neural crest cell differentiation / positive regulation of ubiquitin-protein transferase activity / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / 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 / ion channel inhibitor activity / protein kinase A binding / pigmentation / Ribosomal scanning and start codon recognition / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / 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 / regulation of cell division / SARS-CoV-1 modulates host translation machinery / mTORC1-mediated signalling / cellular response to ethanol / iron-sulfur cluster binding / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / 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 / cellular response to actinomycin D / Response of EIF2AK4 (GCN2) to amino acid deficiency / positive regulation of signal transduction by p53 class mediator / negative regulation of ubiquitin-dependent protein catabolic process / SRP-dependent cotranslational protein targeting to membrane / protein serine/threonine kinase inhibitor activity / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / Major pathway of rRNA processing in the nucleolus and cytosol 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 Å | ||||||
![]() | Li, X. / Wang, M. / Denk, T. / 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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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 4.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 2.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.4 MB | 表示 | |
XML形式データ | ![]() | 346.5 KB | 表示 | |
CIF形式データ | ![]() | 615.8 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 | ![]() 39455MC ![]() 8k2aC ![]() 8k2bC ![]() 8k2cC ![]() 8k2dC ![]() 8k82C ![]() 8xsxC ![]() 8xsyC ![]() 8xszC ![]() 8xt0C ![]() 8xt1C ![]() 8xt2C ![]() 8xt3C ![]() 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 , 4種, 4分子 L5L7L8S2
#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) ![]() |
#48: RNA鎖 | 分子量: 602752.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+60S ribosomal protein ... , 41種, 41分子 LALBLCLDLELFLGLHLJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLeLf...
-Large ribosomal subunit protein ... , 3種, 3分子 LILmLs
#12: タンパク質 | 分子量: 24630.061 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#41: タンパク質 | 分子量: 14771.411 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#46: 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) ![]() |
+40S ribosomal protein ... , 31種, 31分子 SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-タンパク質 , 2種, 2分子 SgSf
#69: 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) ![]() |
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#81: 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) ![]() |
-非ポリマー , 3種, 271分子 




#82: 化合物 | ChemComp-MG / #83: 化合物 | ChemComp-T1C / #84: 化合物 | ChemComp-ZN / |
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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 100um tigecycline / タイプ: RIBOSOME / Entity ID: #1-#81 / 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 / グリッドのタイプ: Quantifoil R3/3 |
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: 44 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (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: cryoSPARC / タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||
3次元再構成 | 解像度: 2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 310531 / 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 |