+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-40344 | ||||||||||||
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タイトル | Terminating ribosome with SRI-41315 | ||||||||||||
マップデータ | unsharpened map | ||||||||||||
試料 |
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キーワード | termination / SRI-41315 / RIBOSOME | ||||||||||||
機能・相同性 | 機能・相同性情報 translation termination factor activity / translation release factor complex / cytoplasmic translational termination / translation release factor activity / regulation of translational termination / translation release factor activity, codon specific / protein methylation / sequence-specific mRNA binding / aminoacyl-tRNA hydrolase activity / regulation of G1 to G0 transition ...translation termination factor activity / translation release factor complex / cytoplasmic translational termination / translation release factor activity / regulation of translational termination / translation release factor activity, codon specific / protein methylation / sequence-specific mRNA binding / aminoacyl-tRNA hydrolase activity / regulation of G1 to G0 transition / laminin receptor activity / exit from mitosis / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / 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 / retinal ganglion cell axon guidance / mammalian oogenesis stage / G1 to G0 transition / activation-induced cell death of T cells / Protein hydroxylation / positive regulation of signal transduction by p53 class mediator / Eukaryotic Translation Termination / phagocytic cup / ubiquitin ligase inhibitor activity / ribosomal small subunit binding / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / T cell proliferation involved in immune response / protein-RNA complex assembly / erythrocyte development / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / negative regulation of ubiquitin-dependent protein catabolic process / ribosomal subunit export from nucleus / translation regulator activity / cellular response to actinomycin D / ribosomal small subunit export from nucleus / translational termination / cytosolic ribosome / laminin binding / 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) / rough endoplasmic reticulum / gastrulation / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / maturation of LSU-rRNA / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / cellular response to leukemia inhibitory factor / maturation of SSU-rRNA / placenta development / small-subunit processome / positive regulation of translation / translational initiation / protein kinase C binding / positive regulation of protein-containing complex assembly / G1/S transition of mitotic cell cycle / cellular response to gamma radiation / transcription coactivator binding / mRNA 5'-UTR binding / Regulation of expression of SLITs and ROBOs / modification-dependent protein catabolic process / spindle / cytoplasmic ribonucleoprotein granule / positive regulation of canonical Wnt signaling pathway / rhythmic process / rRNA processing / protein tag activity / antimicrobial humoral immune response mediated by antimicrobial peptide / glucose homeostasis / virus receptor activity / ribosome biogenesis / ribosome binding / retina development in camera-type eye / regulation of translation / heparin binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cell body / T cell differentiation in thymus / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / perikaryon / defense response to Gram-negative bacterium / cytosolic large ribosomal subunit / killing of cells of another organism / cytoplasmic translation / cell differentiation 類似検索 - 分子機能 | ||||||||||||
生物種 | Oryctolagus cuniculus (ウサギ) / 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: 2.5 Å | ||||||||||||
データ登録者 | Yip MCJ / Coelho JPL / Oltion K / Tauton J / Shao S | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nat Chem Biol / 年: 2024 タイトル: The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center. 著者: João P L Coelho / Matthew C J Yip / Keely Oltion / Jack Taunton / Sichen Shao / 要旨: Translation termination is an essential cellular process, which is also of therapeutic interest for diseases that manifest from premature stop codons. In eukaryotes, translation termination requires ...Translation termination is an essential cellular process, which is also of therapeutic interest for diseases that manifest from premature stop codons. In eukaryotes, translation termination requires eRF1, which recognizes stop codons, catalyzes the release of nascent proteins from ribosomes and facilitates ribosome recycling. The small molecule SRI-41315 triggers eRF1 degradation and enhances translational readthrough of premature stop codons. However, the mechanism of action of SRI-41315 on eRF1 and translation is not known. Here we report cryo-EM structures showing that SRI-41315 acts as a metal-dependent molecular glue between the N domain of eRF1 responsible for stop codon recognition and the ribosomal subunit interface near the decoding center. Retention of eRF1 on ribosomes by SRI-41315 leads to ribosome collisions, eRF1 ubiquitylation and a higher frequency of translation termination at near-cognate stop codons. Our findings reveal a new mechanism of release factor inhibition and additional implications for pharmacologically targeting eRF1. | ||||||||||||
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_40344.map.gz | 335.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-40344-v30.xml emd-40344.xml | 110.8 KB 110.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_40344_fsc.xml | 16.9 KB | 表示 | FSCデータファイル |
画像 | emd_40344.png | 150.7 KB | ||
Filedesc metadata | emd-40344.cif.gz | 22.3 KB | ||
その他 | emd_40344_additional_1.map.gz emd_40344_additional_2.map.gz emd_40344_half_map_1.map.gz emd_40344_half_map_2.map.gz | 101.1 MB 356.6 MB 337.3 MB 337.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-40344 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40344 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_40344_validation.pdf.gz | 1.1 MB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_40344_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | emd_40344_validation.xml.gz | 24.6 KB | 表示 | |
CIF形式データ | emd_40344_validation.cif.gz | 32.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40344 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40344 | HTTPS FTP |
-関連構造データ
関連構造データ | 8scbMC 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 (文献) |
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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_40344.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 | unsharpened map | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.825 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: sharpened map
ファイル | emd_40344_additional_1.map | ||||||||||||
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注釈 | sharpened map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: deepEMhancer processed map
ファイル | emd_40344_additional_2.map | ||||||||||||
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注釈 | deepEMhancer processed map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half2
ファイル | emd_40344_half_map_1.map | ||||||||||||
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注釈 | half2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: half1
ファイル | emd_40344_half_map_2.map | ||||||||||||
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注釈 | half1 | ||||||||||||
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 : terminating rabbit ribosome
+超分子 #1: terminating rabbit ribosome
+分子 #1: Ribosomal protein L8
+分子 #2: Ribosomal protein L3
+分子 #3: 60S ribosomal protein L4
+分子 #4: Ribosomal_L18_c domain-containing protein
+分子 #5: 60S ribosomal protein L6
+分子 #6: 60S ribosomal protein L7
+分子 #7: 60S ribosomal protein L7a
+分子 #8: 60S ribosomal protein L9
+分子 #9: 60S ribosomal protein L10
+分子 #10: 60S ribosomal protein L11
+分子 #11: eL13
+分子 #12: 60S ribosomal protein L14
+分子 #13: Ribosomal protein L15
+分子 #14: uL13
+分子 #15: uL22
+分子 #16: Ribosomal protein L18
+分子 #17: Ribosomal protein L19
+分子 #18: eL20
+分子 #19: eL21
+分子 #20: eL22
+分子 #21: Ribosomal protein L23
+分子 #22: 60S ribosomal protein L24
+分子 #23: eL23
+分子 #24: uL24
+分子 #25: 60S ribosomal protein L27
+分子 #26: 60S ribosomal protein L27a
+分子 #27: 60S ribosomal protein L29
+分子 #28: eL30
+分子 #29: eL31
+分子 #30: eL32
+分子 #31: eL33
+分子 #32: 60S ribosomal protein L34
+分子 #33: eL35
+分子 #34: 60S ribosomal protein L36
+分子 #35: Ribosomal protein L37
+分子 #36: 60S ribosomal protein L38
+分子 #37: eL39
+分子 #38: Ubiquitin A-52 residue ribosomal protein fusion product 1
+分子 #39: eL41
+分子 #40: eL42
+分子 #41: eL43
+分子 #42: eL28
+分子 #43: 60S acidic ribosomal protein P0
+分子 #44: 60S ribosomal protein L12
+分子 #45: NC
+分子 #52: uS2 (SA)
+分子 #53: eS1
+分子 #54: uS5
+分子 #55: Ribosomal protein S3
+分子 #56: eS4 (S4 X isoform)
+分子 #57: uS7
+分子 #58: eS6
+分子 #59: eS7
+分子 #60: eS8
+分子 #61: uS4
+分子 #62: S10_plectin domain-containing protein
+分子 #63: uS17
+分子 #64: eS12
+分子 #65: uS15
+分子 #66: uS11
+分子 #67: uS19
+分子 #68: uS9
+分子 #69: eS17
+分子 #70: uS13
+分子 #71: eS19
+分子 #72: uS10
+分子 #73: eS21
+分子 #74: uS8
+分子 #75: uS12
+分子 #76: 40S ribosomal protein S24
+分子 #77: eS25
+分子 #78: 40S ribosomal protein S26
+分子 #79: eS27
+分子 #80: eS28
+分子 #81: uS14
+分子 #82: eS30
+分子 #83: eS31
+分子 #84: Receptor for Activated C Kinase 1 (RACK1)
+分子 #86: Eukaryotic peptide chain release factor subunit 1
+分子 #87: ATP binding cassette subfamily E member 1
+分子 #46: P_tRNA
+分子 #47: E_tRNA
+分子 #48: 28S_rRNA
+分子 #49: 5S_rRNA
+分子 #50: 5.8S_rRNA
+分子 #51: 18S_rRNA
+分子 #85: mRNA
+分子 #88: MAGNESIUM ION
+分子 #89: ZINC ION
+分子 #90: (2S,4aS)-2-cyclobutyl-10-methyl-3-phenyl-2,10-dihydropyrimido[4,5...
+分子 #91: IRON/SULFUR CLUSTER
+分子 #92: 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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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: 7.5 |
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凍結 | 凍結剤: ETHANE |
-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: GATAN K3 (6k x 4k) / 平均電子線量: 53.8 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): 2.0 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |