+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8pmq | ||||||||||||
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タイトル | Catalytic module of yeast GID E3 ligase bound to multiphosphorylated Ubc8~ubiquitin | ||||||||||||
要素 |
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キーワード | LIGASE / E3 ubiquitin ligase / E2 ubiquitin-conjugating enzyme / phosphorylation / GID | ||||||||||||
機能・相同性 | 機能・相同性情報 GID complex / E2 ubiquitin-conjugating enzyme / ubiquitin conjugating enzyme activity / negative regulation of gluconeogenesis / 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 ...GID complex / E2 ubiquitin-conjugating enzyme / ubiquitin conjugating enzyme activity / negative regulation of gluconeogenesis / 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 / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / TCF dependent signaling in response to WNT / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / Regulation of NF-kappa B signaling / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / NOTCH3 Activation and Transmission of Signal to the Nucleus / Negative regulators of DDX58/IFIH1 signaling / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Fanconi Anemia Pathway / Hh mutants are degraded by ERAD / Negative regulation of FGFR3 signaling / Peroxisomal protein import / Recognition of DNA damage by PCNA-containing replication complex / Degradation of AXIN / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Regulation of TNFR1 signaling / Negative regulation of FGFR2 signaling / Termination of translesion DNA synthesis / Defective CFTR causes cystic fibrosis / Negative regulation of FGFR4 signaling / Hedgehog ligand biogenesis / Stabilization of p53 / EGFR downregulation / Negative regulation of NOTCH4 signaling / Negative regulation of FGFR1 signaling / Iron uptake and transport 類似検索 - 分子機能 | ||||||||||||
生物種 | Saccharomyces cerevisiae (パン酵母) 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: 3.53 Å | ||||||||||||
データ登録者 | Chrustowicz, J. / Sherpa, D. / Prabu, R.J. / Schulman, B.A. | ||||||||||||
資金援助 | ドイツ, European Union, 3件
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引用 | ジャーナル: Mol Cell / 年: 2024 タイトル: Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies. 著者: Jakub Chrustowicz / Dawafuti Sherpa / Jerry Li / Christine R Langlois / Eleftheria C Papadopoulou / D Tung Vu / Laura A Hehl / Özge Karayel / Viola Beier / Susanne von Gronau / Judith ...著者: Jakub Chrustowicz / Dawafuti Sherpa / Jerry Li / Christine R Langlois / Eleftheria C Papadopoulou / D Tung Vu / Laura A Hehl / Özge Karayel / Viola Beier / Susanne von Gronau / Judith Müller / J Rajan Prabu / Matthias Mann / Gary Kleiger / Arno F Alpi / Brenda A Schulman / 要旨: Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ...Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryoelectron microscopy (cryo-EM), biochemistry, and cell biology reveal this exquisitely specific E3-E2 pairing through an unconventional catalytic assembly and auxiliary interactions 70-100 Å away, mediated by E2 multisite phosphorylation. Rather than dynamic polyelectrostatic interactions reported for other ubiquitylation complexes, multiple Ubc8/UBE2H phosphorylation sites within acidic CK2-targeted sequences specifically anchor the E2 C termini to E3 basic patches. Positions of phospho-dependent interactions relative to the catalytic domains correlate across evolution. Overall, our data show that phosphorylation-dependent multivalency establishes a specific E3-E2 partnership, is antagonistic with dephosphorylation, rigidifies the catalytic centers within a flexing GID E3-substrate assembly, and facilitates substrate collision with ubiquitylation active sites. | ||||||||||||
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 | 8pmq.cif.gz | 192.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8pmq.ent.gz | 145.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8pmq.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 | 8pmq_validation.pdf.gz | 1014.1 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8pmq_full_validation.pdf.gz | 1021.7 KB | 表示 | |
XML形式データ | 8pmq_validation.xml.gz | 41.5 KB | 表示 | |
CIF形式データ | 8pmq_validation.cif.gz | 62.2 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/pm/8pmq ftp://data.pdbj.org/pub/pdb/validation_reports/pm/8pmq | HTTPS FTP |
-関連構造データ
関連構造データ | 17764MC 8pjnC C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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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
#1: タンパク質 | 分子量: 49244.594 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Saccharomyces cerevisiae (パン酵母) 遺伝子: RMD5, GID2, YDR255C, YD9320A.05c / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q12508, RING-type E3 ubiquitin transferase | ||
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#2: タンパク質 | 分子量: 59975.102 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) Saccharomyces cerevisiae (パン酵母) 遺伝子: FYV10, GID9, YIL097W / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P40492, RING-type E3 ubiquitin transferase | ||
#3: タンパク質 | 分子量: 24920.771 Da / 分子数: 1 / Mutation: C85K / 由来タイプ: 組換発現 由来: (組換発現) Saccharomyces cerevisiae (パン酵母) 遺伝子: UBC8, GID3, YEL012W / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P28263, E2 ubiquitin-conjugating enzyme | ||
#4: タンパク質 | 分子量: 8576.831 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: UBC / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P0CG48 | ||
#5: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
-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: Complex of yeast Chelator-GIDSR4 E3 ligase, tetrameric Fbp1 substrate and multiphosphorylated Ubc8~ubiquitin タイプ: COMPLEX 詳細: Map obtained by focus refinement over the catalytic module (Gid2, Gid9) and Ubc8~ubiquitin Entity ID: #1-#4 / 由来: RECOMBINANT |
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分子量 | 値: 1.7 MDa / 実験値: NO |
由来(天然) | 生物種: Saccharomyces cerevisiae (パン酵母) |
由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-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): 2300 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 69.24 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.53 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 80606 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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