+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8g6j | |||||||||
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タイトル | mRNA decoding in human is kinetically and structurally distinct from bacteria (GA state 2) | |||||||||
要素 |
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キーワード | RIBOSOME / Human 80S / tRNA / mRNA eEF1A / eIF5A / tRNA selection | |||||||||
機能・相同性 | 機能・相同性情報 cytoplasmic side of lysosomal membrane / : / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / translation at presynapse ...cytoplasmic side of lysosomal membrane / : / Eukaryotic Translation Elongation / eukaryotic translation elongation factor 1 complex / regulation of chaperone-mediated autophagy / positive regulation by host of viral genome replication / eukaryotic 80S initiation complex / : / negative regulation of protein neddylation / translation at presynapse / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / ribosomal protein import into nucleus / embryonic brain development / protein tyrosine kinase inhibitor activity / positive regulation of respiratory burst involved in inflammatory response / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / oxidized purine DNA binding / neural crest cell differentiation / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / negative regulation of phagocytosis / regulation of establishment of cell polarity / positive regulation of ubiquitin-protein transferase activity / A band / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / alpha-beta T cell differentiation / cytoplasmic side of rough endoplasmic reticulum membrane / regulation of G1 to G0 transition / exit from mitosis / laminin receptor activity / pigmentation / 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 / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / optic nerve development / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / Translation initiation complex formation / cortical actin cytoskeleton / retinal ganglion cell axon guidance / fibroblast growth factor binding / mammalian oogenesis stage / homeostatic process / positive regulation of mitochondrial depolarization / G1 to G0 transition / activation-induced cell death of T cells / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / negative regulation of Wnt signaling pathway / lung morphogenesis / negative regulation of peptidyl-serine phosphorylation / iron-sulfur cluster binding / positive regulation of activated T cell proliferation / monocyte chemotaxis / Protein hydroxylation / regulation of cell division / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / mTORC1-mediated signalling / SARS-CoV-1 modulates host translation machinery / Peptide chain elongation / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Selenocysteine synthesis / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / phagocytic cup / negative regulation of respiratory burst involved in inflammatory response / Response of EIF2AK4 (GCN2) to amino acid deficiency / translational elongation / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein localization to nucleus 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
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: 2.8 Å | |||||||||
データ登録者 | Holm, M. / Natchiar, K.S. / Rundlet, E.J. / Myasnikov, A.G. / Altman, R.B. / Blanchard, S.C. | |||||||||
資金援助 | 1件
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引用 | ジャーナル: Nature / 年: 2023 タイトル: mRNA decoding in human is kinetically and structurally distinct from bacteria. 著者: Mikael Holm / S Kundhavai Natchiar / Emily J Rundlet / Alexander G Myasnikov / Zoe L Watson / Roger B Altman / Hao-Yuan Wang / Jack Taunton / Scott C Blanchard / 要旨: In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives ...In all species, ribosomes synthesize proteins by faithfully decoding messenger RNA (mRNA) nucleotide sequences using aminoacyl-tRNA substrates. Current knowledge of the decoding mechanism derives principally from studies on bacterial systems. Although key features are conserved across evolution, eukaryotes achieve higher-fidelity mRNA decoding than bacteria. In human, changes in decoding fidelity are linked to ageing and disease and represent a potential point of therapeutic intervention in both viral and cancer treatment. Here we combine single-molecule imaging and cryogenic electron microscopy methods to examine the molecular basis of human ribosome fidelity to reveal that the decoding mechanism is both kinetically and structurally distinct from that of bacteria. Although decoding is globally analogous in both species, the reaction coordinate of aminoacyl-tRNA movement is altered on the human ribosome and the process is an order of magnitude slower. These distinctions arise from eukaryote-specific structural elements in the human ribosome and in the elongation factor eukaryotic elongation factor 1A (eEF1A) that together coordinate faithful tRNA incorporation at each mRNA codon. The distinct nature and timing of conformational changes within the ribosome and eEF1A rationalize how increased decoding fidelity is achieved and potentially regulated in eukaryotic species. | |||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8g6j.cif.gz | 5 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8g6j.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 8g6j.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 8g6j_validation.pdf.gz | 2.8 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8g6j_full_validation.pdf.gz | 3 MB | 表示 | |
XML形式データ | 8g6j_validation.xml.gz | 416.3 KB | 表示 | |
CIF形式データ | 8g6j_validation.cif.gz | 686.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/g6/8g6j ftp://data.pdbj.org/pub/pdb/validation_reports/g6/8g6j | HTTPS FTP |
-関連構造データ
関連構造データ | 29771MC 8g5yC 8g5zC 8g60C 8g61C 8glpC 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 (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
-集合体
登録構造単位 |
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1 |
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-要素
-RNA鎖 , 7種, 7分子 S2L8L5L7mRAtPt
#1: RNA鎖 | 分子量: 603580.125 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
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#2: RNA鎖 | 分子量: 50171.703 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: GenBank: 555853 |
#3: RNA鎖 | 分子量: 1640884.500 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#4: RNA鎖 | 分子量: 38691.914 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: GenBank: 23898 |
#83: RNA鎖 | 分子量: 19128.443 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#84: RNA鎖 | 分子量: 24634.879 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#85: RNA鎖 | 分子量: 24848.943 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
+40S ribosomal protein ... , 29種, 29分子 SBSASDSJSESCSGSFSHSWSISQSUSKSOSMSSSdSNSLSRSPSTSVSYSZSaSbSc
-タンパク質 , 9種, 9分子 SXSeSfSgLALqLLLmEF
#20: タンパク質 | 分子量: 15860.666 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
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#35: タンパク質 | 分子量: 14415.724 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62861 |
#36: 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) Homo sapiens (ヒト) / 参照: UniProt: P62979 |
#37: 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) Homo sapiens (ヒト) / 参照: UniProt: P63244 |
#39: タンパク質 | 分子量: 28103.855 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#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) Homo sapiens (ヒト) / 参照: UniProt: P05388 |
#49: タンパク質 | 分子量: 31051.576 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#79: タンパク質 | 分子量: 14800.474 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#86: タンパク質 | 分子量: 50368.082 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P68104 |
+60S ribosomal protein ... , 41種, 41分子 LzLBLCLJLHLELGLKLOLVLMLaLNLILDLQLRLSLTLPLULXLYLWLZLrLhLbLFLc...
-非ポリマー , 12種, 406分子
#87: 化合物 | ChemComp-SPD / #88: 化合物 | ChemComp-K / #89: 化合物 | ChemComp-MG / #90: 化合物 | ChemComp-PUT / #91: 化合物 | ChemComp-3HE / | #92: 化合物 | ChemComp-HMT / ( | #93: 化合物 | ChemComp-ZN / #94: 化合物 | ChemComp-PHE / | #95: 化合物 | ChemComp-MET / | #96: 化合物 | ChemComp-GSP / | #97: 化合物 | ChemComp-YRB / ( | #98: 水 | ChemComp-HOH / | |
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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 |
-試料調製
構成要素 | 名称: Human ribosome / タイプ: RIBOSOME / Entity ID: #1-#48, #50-#83, #86 / 由来: NATURAL |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7 |
試料 | 濃度: 4 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 95 % / 凍結前の試料温度: 283 K |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): -1500 nm / 最小 デフォーカス(公称値): -500 nm |
撮影 | 電子線照射量: 79 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING ONLY | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 80708 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: OTHER | ||||||||||||||||||||||||
拘束条件 |
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