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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Human mitochondrial ribosome in complex with antibiotic tigecycline | |||||||||
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![]() | antibiotics / immunometabolism / mitochondrial ribosomes / tetracyclines / T cells. / RIBOSOME | |||||||||
機能・相同性 | ![]() rRNA import into mitochondrion / mitochondrial translational termination / mitochondrial ribosome assembly / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / negative regulation of mitotic nuclear division ...rRNA import into mitochondrion / mitochondrial translational termination / mitochondrial ribosome assembly / mitochondrial translational elongation / Mitochondrial translation elongation / Mitochondrial translation termination / translation release factor activity, codon nonspecific / Mitochondrial translation initiation / translation release factor activity / negative regulation of mitotic nuclear division / mitochondrial large ribosomal subunit / peptidyl-tRNA hydrolase / mitochondrial ribosome / 加水分解酵素; エステル加水分解酵素; 5'-リン酸モノエステル産生エンドリボヌクレアーゼ / mitochondrial small ribosomal subunit / peptidyl-tRNA hydrolase activity / mitochondrial translation / apoptotic mitochondrial changes / positive regulation of proteolysis / ribosomal small subunit binding / anatomical structure morphogenesis / RNA processing / Mitochondrial protein degradation / rescue of stalled ribosome / cellular response to leukemia inhibitory factor / apoptotic signaling pathway / fibrillar center / cell junction / double-stranded RNA binding / regulation of translation / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / large ribosomal subunit rRNA binding / endonuclease activity / nuclear membrane / 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 / tRNA binding / cell population proliferation / mitochondrial inner membrane / negative regulation of translation / rRNA binding / nuclear body / structural constituent of ribosome / ribosome / mitochondrial matrix / translation / ribonucleoprotein complex / protein domain specific binding / nucleotide binding / intracellular membrane-bounded organelle / mRNA binding / apoptotic process / GTP binding / nucleolus / mitochondrion / extracellular space / RNA binding / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm 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: 2.4 Å | |||||||||
![]() | Khawaja A / Nguyen MD / Singh V / Rorbach J | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: T cell toxicity induced by tigecycline binding to the mitochondrial ribosome. 著者: Qiuya Shao / Anas Khawaja / Minh Duc Nguyen / Vivek Singh / Jingdian Zhang / Yong Liu / Joel Nordin / Monika Adori / C Axel Innis / Xaquin Castro Dopico / Joanna Rorbach / ![]() ![]() ![]() ![]() ![]() 要旨: Tetracyclines are essential bacterial protein synthesis inhibitors under continual development to combat antibiotic resistance yet suffer from unwanted side effects. Mitoribosomes - responsible for ...Tetracyclines are essential bacterial protein synthesis inhibitors under continual development to combat antibiotic resistance yet suffer from unwanted side effects. Mitoribosomes - responsible for generating oxidative phosphorylation (OXPHOS) subunits - share structural similarities with bacterial machinery and may suffer from cross-reactivity. Since lymphocytes rely upon OXPHOS upregulation to establish immunity, we set out to assess the impact of ribosome-targeting antibiotics on human T cells. We find tigecycline, a third-generation tetracycline, to be the most cytotoxic compound tested. In vitro, 5-10 μM tigecycline inhibits mitochondrial but not cytosolic translation, mitochondrial complex I, III and IV expression, and curtails the activation and expansion of unique T cell subsets. By cryo-EM, we find tigecycline to occupy three sites on T cell mitoribosomes. In addition to the conserved A-site found in bacteria, tigecycline also attaches to the peptidyl transferase center of the large subunit. Furthermore, a third, distinct binding site on the large subunit, aligns with helices analogous to those in bacteria, albeit lacking methylation in humans. The data provide a mechanism to explain part of the anti-inflammatory effects of these drugs and inform antibiotic design. | |||||||||
履歴 |
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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 56.6 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 110.3 KB 110.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 76.2 KB | ||
Filedesc metadata | ![]() | 22.9 KB | ||
その他 | ![]() | 257.7 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 404.7 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 404.2 KB | 表示 | |
XML形式データ | ![]() | 8.1 KB | 表示 | |
CIF形式データ | ![]() | 9.6 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 | ![]() 8rriMC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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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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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: 1.01 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 P-tRNA Homogenous refinement
ファイル | emd_19460_additional_1.map | ||||||||||||
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注釈 | consensus P-tRNA Homogenous refinement | ||||||||||||
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 : Human mitochondrial ribosome in complex with antibiotic tigecycline
+超分子 #1: Human mitochondrial ribosome in complex with antibiotic tigecycline
+分子 #1: mitochondrial tRNAVal
+分子 #82: E/E-tRNA
+分子 #83: 12S mitochondrial rRNA
+分子 #84: 16S mitochondrial rRNA
+分子 #85: mRNA
+分子 #86: P/P-tRNA
+分子 #2: 39S ribosomal protein L2, mitochondrial
+分子 #3: 39S ribosomal protein L3, mitochondrial
+分子 #4: 39S ribosomal protein L4, mitochondrial
+分子 #5: 39S ribosomal protein L9, mitochondrial
+分子 #6: 39S ribosomal protein L11, mitochondrial
+分子 #7: Large ribosomal subunit protein uL13m
+分子 #8: 39S ribosomal protein L14, mitochondrial
+分子 #9: 39S ribosomal protein L15, mitochondrial
+分子 #10: 39S ribosomal protein L16, mitochondrial
+分子 #11: 39S ribosomal protein L17, mitochondrial
+分子 #12: 39S ribosomal protein L18, mitochondrial
+分子 #13: 39S ribosomal protein L19, mitochondrial
+分子 #14: 39S ribosomal protein L20, mitochondrial
+分子 #15: 39S ribosomal protein L21, mitochondrial
+分子 #16: 39S ribosomal protein L22, mitochondrial
+分子 #17: Large ribosomal subunit protein uL23m
+分子 #18: 39S ribosomal protein L24, mitochondrial
+分子 #19: 39S ribosomal protein L27, mitochondrial
+分子 #20: 39S ribosomal protein L28, mitochondrial
+分子 #21: 39S ribosomal protein L47, mitochondrial
+分子 #22: 39S ribosomal protein L30, mitochondrial
+分子 #23: 39S ribosomal protein L32, mitochondrial
+分子 #24: 39S ribosomal protein L33, mitochondrial
+分子 #25: 39S ribosomal protein L34, mitochondrial
+分子 #26: 39S ribosomal protein L35, mitochondrial
+分子 #27: 39S ribosomal protein L36, mitochondrial
+分子 #28: 39S ribosomal protein L1, mitochondrial
+分子 #29: 39S ribosomal protein L37, mitochondrial
+分子 #30: 39S ribosomal protein L38, mitochondrial
+分子 #31: 39S ribosomal protein L39, mitochondrial
+分子 #32: 39S ribosomal protein L40, mitochondrial
+分子 #33: 39S ribosomal protein L41, mitochondrial
+分子 #34: 39S ribosomal protein L42, mitochondrial
+分子 #35: 39S ribosomal protein L43, mitochondrial
+分子 #36: 39S ribosomal protein L44, mitochondrial
+分子 #37: 39S ribosomal protein L45, mitochondrial
+分子 #38: 39S ribosomal protein L46, mitochondrial
+分子 #39: 39S ribosomal protein L48, mitochondrial
+分子 #40: 39S ribosomal protein L49, mitochondrial
+分子 #41: 39S ribosomal protein L50, mitochondrial
+分子 #42: 39S ribosomal protein L51, mitochondrial
+分子 #43: 39S ribosomal protein L52, mitochondrial
+分子 #44: Large ribosomal subunit protein mL53
+分子 #45: 39S ribosomal protein L54, mitochondrial
+分子 #46: 39S ribosomal protein L55, mitochondrial
+分子 #47: Ribosomal protein 63, mitochondrial
+分子 #48: Peptidyl-tRNA hydrolase ICT1, mitochondrial
+分子 #49: Growth arrest and DNA damage-inducible proteins-interacting protein 1
+分子 #50: 39S ribosomal protein S18a, mitochondrial
+分子 #51: 39S ribosomal protein S30, mitochondrial
+分子 #52: 28S ribosomal protein S2, mitochondrial
+分子 #53: 28S ribosomal protein S24, mitochondrial
+分子 #54: 28S ribosomal protein S5, mitochondrial
+分子 #55: 28S ribosomal protein S6, mitochondrial
+分子 #56: 28S ribosomal protein S7, mitochondrial
+分子 #57: 28S ribosomal protein S9, mitochondrial
+分子 #58: 28S ribosomal protein S10, mitochondrial
+分子 #59: 28S ribosomal protein S11, mitochondrial
+分子 #60: 28S ribosomal protein S12, mitochondrial
+分子 #61: 28S ribosomal protein S14, mitochondrial
+分子 #62: 28S ribosomal protein S15, mitochondrial
+分子 #63: 28S ribosomal protein S16, mitochondrial
+分子 #64: 28S ribosomal protein S17, mitochondrial
+分子 #65: 28S ribosomal protein S18b, mitochondrial
+分子 #66: 28S ribosomal protein S18c, mitochondrial
+分子 #67: Small ribosomal subunit protein bS21m
+分子 #68: 28S ribosomal protein S22, mitochondrial
+分子 #69: 28S ribosomal protein S23, mitochondrial
+分子 #70: Small ribosomal subunit protein mS25
+分子 #71: 28S ribosomal protein S26, mitochondrial
+分子 #72: 28S ribosomal protein S27, mitochondrial
+分子 #73: 28S ribosomal protein S28, mitochondrial
+分子 #74: 28S ribosomal protein S29, mitochondrial
+分子 #75: 28S ribosomal protein S31, mitochondrial
+分子 #76: 28S ribosomal protein S33, mitochondrial
+分子 #77: 28S ribosomal protein S34, mitochondrial
+分子 #78: 28S ribosomal protein S35, mitochondrial
+分子 #79: Small ribosomal subunit protein mS37
+分子 #80: Aurora kinase A-interacting protein
+分子 #81: Pentatricopeptide repeat domain-containing protein 3, mitochondrial
+分子 #87: VALINE
+分子 #88: MAGNESIUM ION
+分子 #89: FE2/S2 (INORGANIC) CLUSTER
+分子 #90: ADENOSINE-5'-TRIPHOSPHATE
+分子 #91: GUANOSINE-5'-DIPHOSPHATE
+分子 #92: TIGECYCLINE
+分子 #93: POTASSIUM ION
+分子 #94: water
-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: 7.5 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 45.0 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): 1.6 µm / 最小 デフォーカス(公称値): 0.4 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |