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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: 8qfd | |||||||||||||||
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タイトル | UFL1 E3 ligase bound 60S ribosome | |||||||||||||||
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![]() | LIGASE / UFM1 / Ribosome / Complex | |||||||||||||||
機能・相同性 | ![]() UFM1 ligase activity / UFM1 transferase activity / protein ufmylation / protein K69-linked ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / embryonic brain development / regulation of intracellular estrogen receptor signaling pathway / eukaryotic 80S initiation complex / negative regulation of protein neddylation ...UFM1 ligase activity / UFM1 transferase activity / protein ufmylation / protein K69-linked ufmylation / negative regulation of IRE1-mediated unfolded protein response / regulation of proteasomal ubiquitin-dependent protein catabolic process / embryonic brain development / regulation of intracellular estrogen receptor signaling pathway / eukaryotic 80S initiation complex / negative regulation of protein neddylation / translation at presynapse / axial mesoderm development / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / 90S preribosome assembly / TORC2 complex binding / 転移酵素; アシル基を移すもの; アミノアシル基を移すもの / GAIT complex / middle ear morphogenesis / regulation of canonical NF-kappaB signal transduction / reticulophagy / cytoplasmic side of rough endoplasmic reticulum membrane / A band / alpha-beta T cell differentiation / 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 / response to L-glutamate / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of ubiquitin protein ligase activity / optic nerve development / response to aldosterone / retinal ganglion cell axon guidance / G1 to G0 transition / homeostatic process / negative regulation of NF-kappaB transcription factor activity / lung morphogenesis / Protein hydroxylation / macrophage chemotaxis / Peptide chain elongation / 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 / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / protein localization to nucleus / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / hematopoietic stem cell differentiation / Major pathway of rRNA processing in the nucleolus and cytosol / protein-RNA complex assembly / protein targeting / cellular response to interleukin-4 / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / translation regulator activity / positive regulation of autophagy / cellular response to actinomycin D / cytosolic ribosome / rough endoplasmic reticulum / Maturation of protein E / positive regulation of glial cell proliferation / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / negative regulation of protein ubiquitination / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / negative regulation of ubiquitin-dependent protein catabolic process / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy 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: 2.2 Å | |||||||||||||||
![]() | Makhlouf, L. / Kulathu, Y. / Zeqiraj, E. | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons. 著者: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas ...著者: Linda Makhlouf / Joshua J Peter / Helge M Magnussen / Rohan Thakur / David Millrine / Thomas C Minshull / Grace Harrison / Joby Varghese / Frederic Lamoliatte / Martina Foglizzo / Thomas Macartney / Antonio N Calabrese / Elton Zeqiraj / Yogesh Kulathu / ![]() 要旨: Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, ...Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24). This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. ). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S-SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a 'writer' to a 'reader' module that recognizes its product-UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER. | |||||||||||||||
履歴 |
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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 | ![]() | 3.1 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.6 MB | 表示 | |
XML形式データ | ![]() | 193.4 KB | 表示 | |
CIF形式データ | ![]() | 357.4 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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 , 3種, 3分子 578
#1: RNA鎖 | 分子量: 1640230.250 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: 38385.750 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) ![]() |
+60S ribosomal protein ... , 38種, 38分子 ABCDEGHIJLMNOPQRSTUVWXYZabcdef...
-タンパク質 , 4種, 4分子 Fjms
#9: タンパク質 | 分子量: 29290.973 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#38: タンパク質 | 分子量: 11111.032 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#41: タンパク質 | 分子量: 14758.394 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#45: タンパク質 | 分子量: 91591.234 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() 参照: UniProt: O94874, 転移酵素; アシル基を移すもの; アミノアシル基を移すもの |
-非ポリマー , 3種, 2330分子 ![](data/chem/img/MG.gif)
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![](data/chem/img/HOH.gif)
![](data/chem/img/ZN.gif)
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#46: 化合物 | ChemComp-MG / #47: 化合物 | ChemComp-ZN / #48: 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 | N |
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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 |
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由来(天然) |
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由来(組換発現) | 生物種: ![]() ![]() | ||||||||||||||||||
緩衝液 | pH: 7.5 / 詳細: 25 mM HEPES pH 7.5, 50 mM KCl, 5 mM MgCl2, 2 mM DTT | ||||||||||||||||||
試料 | 濃度: 7.7 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: 100 % / 凍結前の試料温度: 277 K |
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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 / 倍率(公称値): 165000 X / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 200 nm |
撮影 | 平均露光時間: 2.67 sec. / 電子線照射量: 33.4 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 撮影したグリッド数: 1 / 実像数: 59394 |
電子光学装置 | エネルギーフィルター名称: TFS Selectris X / エネルギーフィルタースリット幅: 10 eV |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
3次元再構成 | 解像度: 2.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 299008 / 対称性のタイプ: POINT |