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基本情報
登録情報 | データベース: PDB / ID: 7ay1 | |||||||||
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タイトル | Cryo-EM structure of USP1-UAF1 bound to mono-ubiquitinated FANCD2, and FANCI | |||||||||
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![]() | HYDROLASE / deubiquitination / specificity / DNA repair / Fanconi Anemia | |||||||||
機能・相同性 | ![]() positive regulation of error-prone translesion synthesis / regulation of protein monoubiquitination / Signaling by cytosolic PDGFRA and PDGFRB fusion proteins / regulation of CD40 signaling pathway / regulation of regulatory T cell differentiation / monoubiquitinated protein deubiquitination / double-strand break repair involved in meiotic recombination / homologous chromosome pairing at meiosis / gamete generation / neuronal stem cell population maintenance ...positive regulation of error-prone translesion synthesis / regulation of protein monoubiquitination / Signaling by cytosolic PDGFRA and PDGFRB fusion proteins / regulation of CD40 signaling pathway / regulation of regulatory T cell differentiation / monoubiquitinated protein deubiquitination / double-strand break repair involved in meiotic recombination / homologous chromosome pairing at meiosis / gamete generation / neuronal stem cell population maintenance / brain morphogenesis / deubiquitinase activator activity / DNA repair complex / skeletal system morphogenesis / mitotic intra-S DNA damage checkpoint signaling / skin development / seminiferous tubule development / protein deubiquitination / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Viral mRNA Translation / positive regulation of double-strand break repair via homologous recombination / homeostasis of number of cells / L13a-mediated translational silencing of Ceruloplasmin expression / GTP hydrolysis and joining of the 60S ribosomal subunit / single fertilization / Major pathway of rRNA processing in the nucleolus and cytosol / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / embryonic organ development / regulation of DNA repair / interstrand cross-link repair / cytosolic ribosome / DNA polymerase binding / response to UV / condensed chromosome / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / 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 / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / TNFR1-induced NF-kappa-B signaling pathway / APC/C:Cdc20 mediated degradation of Securin / ubiquitin binding / positive regulation of protein ubiquitination / Asymmetric localization of PCP proteins 類似検索 - 分子機能 | |||||||||
生物種 | ![]() synthetic construct (人工物) | |||||||||
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: 3.7 Å | |||||||||
![]() | Rennie, M.L. / Arkinson, C. / Walden, H. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis of FANCD2 deubiquitination by USP1-UAF1. 著者: Martin L Rennie / Connor Arkinson / Viduth K Chaugule / Rachel Toth / Helen Walden / ![]() 要旨: Ubiquitin-specific protease 1 (USP1) acts together with the cofactor UAF1 during DNA repair processes to specifically remove monoubiquitin signals. One substrate of the USP1-UAF1 complex is the ...Ubiquitin-specific protease 1 (USP1) acts together with the cofactor UAF1 during DNA repair processes to specifically remove monoubiquitin signals. One substrate of the USP1-UAF1 complex is the monoubiquitinated FANCI-FANCD2 heterodimer, which is involved in the repair of DNA interstrand crosslinks via the Fanconi anemia pathway. Here we determine structures of human USP1-UAF1 with and without ubiquitin and bound to monoubiquitinated FANCI-FANCD2. The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases. A cryo-EM reconstruction of USP1-UAF1 in complex with monoubiquitinated FANCI-FANCD2 highlights a highly orchestrated deubiquitination process, with USP1-UAF1 driving conformational changes in the substrate. An extensive interface between UAF1 and FANCI, confirmed by mutagenesis and biochemical assays, provides a molecular explanation for the requirement of both proteins, despite neither being directly involved in catalysis. Overall, our data provide molecular details of USP1-UAF1 regulation and substrate recognition. #1: ![]() タイトル: Structural basis of FANCD2 deubiquitination by USP1-UAF1 著者: Rennie, M.L. / Arkinson, C. / Chaugule, V.K. / Toth, R. / Walden, H. | |||||||||
履歴 |
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構造の表示
ムービー |
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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 | ![]() | 590.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 463.4 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.5 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.5 MB | 表示 | |
XML形式データ | ![]() | 92.6 KB | 表示 | |
CIF形式データ | ![]() | 139.7 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
-Fanconi anemia group ... , 2種, 2分子 AB
#1: タンパク質 | 分子量: 150459.125 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q9NVI1 |
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#2: タンパク質 | 分子量: 164623.828 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q9BXW9 |
-タンパク質 , 3種, 3分子 CDE
#3: タンパク質 | 分子量: 8875.125 Da / 分子数: 1 / Mutation: GPGS expression tag / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P62987 |
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#4: タンパク質 | 分子量: 88390.273 Da / 分子数: 1 / Mutation: C90S, G670A, G671A / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: O94782, ubiquitinyl hydrolase 1 |
#5: タンパク質 | 分子量: 78300.656 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q8TAF3 |
-DNA鎖 / 非ポリマー , 2種, 3分子 ST![](data/chem/img/ZN.gif)
![](data/chem/img/ZN.gif)
#6: DNA鎖 | 分子量: 5177.820 Da / 分子数: 2 / 由来タイプ: 合成 詳細: Arbitrary DNA sequence modelled due to insufficient local resolution to determine sequence register. DNA used TGATCAGAGGTCATTTGAATTCATGGCTTCGAGCTTCATGTAGAGTCGACGGTGCTGGGAT 由来: (合成) synthetic construct (人工物) #7: 化合物 | ChemComp-ZN / | |
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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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分子量 | 値: 0.49 MDa / 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 4.3 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: 288 K |
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電子顕微鏡撮影
顕微鏡 | モデル: JEOL CRYO ARM 300 |
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電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 平均露光時間: 14.9 sec. / 電子線照射量: 65 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: DIRECT ELECTRON DE-64 (8k x 8k) |
画像スキャン | 動画フレーム数/画像: 59 |
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解析
ソフトウェア | 名称: PHENIX / バージョン: (1.18_3855:phenix.real_space_refine) / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 249732 | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 391552 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: THROUGHOUT | ||||||||||||||||||||||||
原子変位パラメータ | Biso max: 370.07 Å2 / Biso mean: 65.7212 Å2 / Biso min: 17.11 Å2 | ||||||||||||||||||||||||
拘束条件 |
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