+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-44463 | |||||||||
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タイトル | 80S ribosome with angiogenin and tRNAAla | |||||||||
マップデータ | 80S ribosome with angiogenin with cleaved tRNA | |||||||||
試料 |
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キーワード | Angiogenin / RNase / RIBOSOME | |||||||||
機能・相同性 | 機能・相同性情報 activation of phospholipase A2 activity / angiogenin-PRI complex / diacylglycerol biosynthetic process / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / tRNA decay / cell communication / ribosomal subunit / 加水分解酵素; エステル加水分解酵素; 3'-リン酸モノエステル産生エンドリボヌクレアーゼ / Adherens junctions interactions / oocyte maturation ...activation of phospholipase A2 activity / angiogenin-PRI complex / diacylglycerol biosynthetic process / tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis / tRNA decay / cell communication / ribosomal subunit / 加水分解酵素; エステル加水分解酵素; 3'-リン酸モノエステル産生エンドリボヌクレアーゼ / Adherens junctions interactions / oocyte maturation / regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / mammalian oogenesis stage / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / activation-induced cell death of T cells / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / rRNA transcription / phagocytic cup / : / basement membrane / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / protein-RNA complex assembly / RNA nuclease activity / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / cellular response to actinomycin D / cytosolic ribosome / ovarian follicle development / rough endoplasmic reticulum / positive regulation of phosphorylation / 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) / gastrulation / MDM2/MDM4 family protein binding / positive regulation of endothelial cell proliferation / RNA endonuclease activity / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / activation of protein kinase B activity / negative regulation of ubiquitin-dependent protein catabolic process / actin filament polymerization / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to hormone / maturation of LSU-rRNA / ribosomal large subunit biogenesis / cellular response to leukemia inhibitory factor / maturation of SSU-rRNA / positive regulation of translation / positive regulation of protein secretion / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / peptide binding / negative regulation of smooth muscle cell proliferation / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / cytoplasmic ribonucleoprotein granule / spindle / G1/S transition of mitotic cell cycle / rRNA processing / antimicrobial humoral immune response mediated by antimicrobial peptide / large ribosomal subunit / rhythmic process / cell migration / actin cytoskeleton / positive regulation of canonical Wnt signaling pathway / ribosome biogenesis / ribosome binding / glucose homeostasis / retina development in camera-type eye / regulation of translation / chromosome / ribosomal small subunit biogenesis / heparin binding / actin binding / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cell body / growth cone / antibacterial humoral response / T cell differentiation in thymus / 5S rRNA binding 類似検索 - 分子機能 | |||||||||
生物種 | Oryctolagus cuniculus (ウサギ) / Escherichia coli (大腸菌) / Homo sapiens (ヒト) / 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: 3.1 Å | |||||||||
データ登録者 | Loveland AB / Korostelev AA | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Structural mechanism of angiogenin activation by the ribosome. 著者: Anna B Loveland / Cha San Koh / Robin Ganesan / Allan Jacobson / Andrei A Korostelev / 要旨: Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance. After activation during cellular stress, ...Angiogenin, an RNase-A-family protein, promotes angiogenesis and has been implicated in cancer, neurodegenerative diseases and epigenetic inheritance. After activation during cellular stress, angiogenin cleaves tRNAs at the anticodon loop, resulting in translation repression. However, the catalytic activity of isolated angiogenin is very low, and the mechanisms of the enzyme activation and tRNA specificity have remained a puzzle. Here we identify these mechanisms using biochemical assays and cryogenic electron microscopy (cryo-EM). Our study reveals that the cytosolic ribosome is the activator of angiogenin. A cryo-EM structure features angiogenin bound in the A site of the 80S ribosome. The C-terminal tail of angiogenin is rearranged by interactions with the ribosome to activate the RNase catalytic centre, making the enzyme several orders of magnitude more efficient in tRNA cleavage. Additional 80S-angiogenin structures capture how tRNA substrate is directed by the ribosome into angiogenin's active site, demonstrating that the ribosome acts as the specificity factor. Our findings therefore suggest that angiogenin is activated by ribosomes with a vacant A site, the abundance of which increases during cellular stress. These results may facilitate the development of therapeutics to treat cancer and neurodegenerative diseases. | |||||||||
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_44463.map.gz | 794.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-44463-v30.xml emd-44463.xml | 108 KB 108 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_44463_fsc.xml | 20.6 KB | 表示 | FSCデータファイル |
画像 | emd_44463.png | 185.6 KB | ||
Filedesc metadata | emd-44463.cif.gz | 19.6 KB | ||
その他 | emd_44463_half_map_1.map.gz emd_44463_half_map_2.map.gz | 144.8 MB 144.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-44463 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44463 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_44463_validation.pdf.gz | 967.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_44463_full_validation.pdf.gz | 966.8 KB | 表示 | |
XML形式データ | emd_44463_validation.xml.gz | 30.1 KB | 表示 | |
CIF形式データ | emd_44463_validation.cif.gz | 39.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44463 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44463 | HTTPS FTP |
-関連構造データ
関連構造データ | 9bdnMC 9bdlC 9bdpC C: 同じ文献を引用 (文献) 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_44463.map.gz / 形式: CCP4 / 大きさ: 857.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | 80S ribosome with angiogenin with cleaved tRNA | ||||||||||||||||||||||||||||||||||||
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: 0.87 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
-ハーフマップ: 80S ribosome with angiogenin with cleaved tRNA, half map 1
ファイル | emd_44463_half_map_1.map | ||||||||||||
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注釈 | 80S ribosome with angiogenin with cleaved tRNA, half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: 80S ribosome with angiogenin with cleaved tRNA, half map 1
ファイル | emd_44463_half_map_2.map | ||||||||||||
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注釈 | 80S ribosome with angiogenin with cleaved tRNA, half map 1 | ||||||||||||
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 : 80S ribosome with angiogenin and tRNAAla
+超分子 #1: 80S ribosome with angiogenin and tRNAAla
+分子 #1: 18S rRNA
+分子 #2: 28S rRNA
+分子 #3: 5.8S rRNA
+分子 #4: 5S rRNA
+分子 #82: tRNAfMet
+分子 #83: mRNA
+分子 #84: tRNAAla
+分子 #5: 60S ribosomal protein L8
+分子 #6: 60S ribosomal protein L3
+分子 #7: 60S ribosomal protein L4
+分子 #8: 60S ribosomal protein L5
+分子 #9: 60S ribosomal protein L6
+分子 #10: 60S ribosomal protein L7
+分子 #11: Large ribosomal subunit protein eL8
+分子 #12: 60S ribosomal protein L9
+分子 #13: Ribosomal protein L10
+分子 #14: 60S ribosomal protein L11
+分子 #15: uL11
+分子 #16: Large ribosomal subunit protein eL13
+分子 #17: 60S ribosomal protein L14
+分子 #18: 60S ribosomal protein L15
+分子 #19: Large ribosomal subunit protein uL13
+分子 #20: 60S ribosomal protein L17
+分子 #21: Large ribosomal subunit protein eL18
+分子 #22: 60S ribosomal protein L19
+分子 #23: 60S ribosomal protein L18a
+分子 #24: 60S ribosomal protein L21
+分子 #25: Large ribosomal subunit protein eL22
+分子 #26: 60S ribosomal protein L23
+分子 #27: Ribosomal protein L24
+分子 #28: Large ribosomal subunit protein uL23
+分子 #29: 60S ribosomal protein L26
+分子 #30: 60S ribosomal protein L27
+分子 #31: 60S ribosomal protein L27a
+分子 #32: Large ribosomal subunit protein eL29
+分子 #33: 60S ribosomal protein L30
+分子 #34: 60S ribosomal protein L31
+分子 #35: Large ribosomal subunit protein eL32
+分子 #36: 60S ribosomal protein L35a
+分子 #37: 60S ribosomal protein L34
+分子 #38: 60S ribosomal protein L35
+分子 #39: 60S ribosomal protein L36
+分子 #40: 60S ribosomal protein L37
+分子 #41: Large ribosomal subunit protein eL38
+分子 #42: 60S ribosomal protein L39
+分子 #43: Large ribosomal subunit protein eL40
+分子 #44: eL41
+分子 #45: eL42
+分子 #46: 60S ribosomal protein L37a
+分子 #47: 60S ribosomal protein L28
+分子 #48: 60S acidic ribosomal protein P0
+分子 #49: Angiogenin
+分子 #50: Receptor of activated protein C kinase 1
+分子 #51: 40S_SA_C domain-containing protein
+分子 #52: 40S ribosomal protein S3a
+分子 #53: 40S ribosomal protein S2
+分子 #54: 40S ribosomal protein S3
+分子 #55: 40S ribosomal protein S4
+分子 #56: Ribosomal protein S5
+分子 #57: 40S ribosomal protein S6
+分子 #58: Small ribosomal subunit protein eS7
+分子 #59: 40S ribosomal protein S8
+分子 #60: 40S ribosomal protein S9
+分子 #61: 40S ribosomal protein S10
+分子 #62: 40S ribosomal protein S11
+分子 #63: 40S ribosomal protein S12
+分子 #64: 40S ribosomal protein S13
+分子 #65: Small ribosomal subunit protein uS11
+分子 #66: 40S ribosomal protein S15
+分子 #67: Small ribosomal subunit protein uS9
+分子 #68: 40S ribosomal protein S17
+分子 #69: 40S ribosomal protein S18
+分子 #70: Small ribosomal subunit protein eS19
+分子 #71: 40S ribosomal protein S20
+分子 #72: eS21
+分子 #73: 40S ribosomal protein S15a
+分子 #74: 40S ribosomal protein S23
+分子 #75: 40S ribosomal protein S24
+分子 #76: 40S ribosomal protein S25
+分子 #77: eS26
+分子 #78: 40S ribosomal protein S27
+分子 #79: 40S ribosomal protein S28
+分子 #80: 40S ribosomal protein S29
+分子 #81: 40S ribosomal protein S30
-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 |
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グリッド | モデル: Quantifoil R2/1 / 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 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 278 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 30.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |