+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8u83 | ||||||
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タイトル | KCTD5/Cullin3/Gbeta1gamma2 Complex: State C From Composite RELION Multi-body Refinement Map | ||||||
要素 |
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キーワード | LIGASE (リガーゼ) / cullin family protein / proteasome-mediated ubiquitin-dependent protein catabolic process / complex / ubiquitin-dependent protein catabolic process | ||||||
機能・相同性 | 機能・相同性情報 liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division ...liver morphogenesis / positive regulation of mitotic cell cycle phase transition / trophectodermal cellular morphogenesis / POZ domain binding / nuclear protein quality control by the ubiquitin-proteasome system / regulation protein catabolic process at postsynapse / polar microtubule / anaphase-promoting complex-dependent catabolic process / COPII vesicle coating / stem cell division / RHOBTB3 ATPase cycle / embryonic cleavage / cell projection organization / positive regulation of mitotic metaphase/anaphase transition / Notch binding / RHOBTB1 GTPase cycle / fibroblast apoptotic process / negative regulation of Rho protein signal transduction / negative regulation of type I interferon production / ubiquitin ligase complex scaffold activity / mitotic metaphase chromosome alignment / Cul3-RING ubiquitin ligase complex / stress fiber assembly / positive regulation of cytokinesis / protein monoubiquitination / cullin family protein binding / sperm flagellum / gastrulation / protein autoubiquitination / endoplasmic reticulum to Golgi vesicle-mediated transport / RHOBTB2 GTPase cycle / protein K48-linked ubiquitination / positive regulation of TORC1 signaling / cyclin binding / intrinsic apoptotic signaling pathway / positive regulation of protein ubiquitination / integrin-mediated signaling pathway / Degradation of DVL / cellular response to amino acid stimulus / Hedgehog 'on' state / G1/S transition of mitotic cell cycle / Olfactory Signaling Pathway / protein destabilization / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / protein homooligomerization / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / 紡錘体 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Wntシグナル経路 / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / 紡錘体 / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / Regulation of RAS by GAPs / G beta:gamma signalling through PI3Kgamma / protein polyubiquitination / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / KEAP1-NFE2L2 pathway / G alpha (12/13) signalling events / ubiquitin protein ligase activity / extracellular vesicle / 遊走 / signaling receptor complex adaptor activity / Antigen processing: Ubiquitination & Proteasome degradation / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / Neddylation / phospholipase C-activating G protein-coupled receptor signaling pathway / 遺伝子発現 / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / ubiquitin-dependent protein catabolic process 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: 3.975 Å | ||||||
データ登録者 | Kuntz, D.A. / Nguyen, D.M. / Narayanan, N. / Prive, G.G. | ||||||
資金援助 | カナダ, 1件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2024 タイトル: Structure and dynamics of a pentameric KCTD5/CUL3/Gβγ E3 ubiquitin ligase complex. 著者: Duc Minh Nguyen / Deanna H Rath / Dominic Devost / Darlaine Pétrin / Robert Rizk / Alan X Ji / Naveen Narayanan / Darren Yong / Andrew Zhai / Douglas A Kuntz / Maha U Q Mian / Neil C Pomroy ...著者: Duc Minh Nguyen / Deanna H Rath / Dominic Devost / Darlaine Pétrin / Robert Rizk / Alan X Ji / Naveen Narayanan / Darren Yong / Andrew Zhai / Douglas A Kuntz / Maha U Q Mian / Neil C Pomroy / Alexander F A Keszei / Samir Benlekbir / Mohammad T Mazhab-Jafari / John L Rubinstein / Terence E Hébert / Gilbert G Privé / 要旨: Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C- ...Heterotrimeric G proteins can be regulated by posttranslational modifications, including ubiquitylation. KCTD5, a pentameric substrate receptor protein consisting of an N-terminal BTB domain and a C-terminal domain, engages CUL3 to form the central scaffold of a cullin-RING E3 ligase complex (CRL3) that ubiquitylates Gβγ and reduces Gβγ protein levels in cells. The cryo-EM structure of a 5:5:5 KCTD5/CUL3/Gβγ assembly reveals a highly dynamic complex with rotations of over 60° between the KCTD5/CUL3 and KCTD5/Gβγ moieties of the structure. CRL3 engages the E3 ligase ARIH1 to ubiquitylate Gβγ in an E3-E3 superassembly, and extension of the structure to include full-length CUL3 with RBX1 and an ARIH1~ubiquitin conjugate reveals that some conformational states position the ARIH1~ubiquitin thioester bond to within 10 Å of lysine-23 of Gβ and likely represent priming complexes. Most previously described CRL/substrate structures have consisted of monovalent complexes and have involved flexible peptide substrates. The structure of the KCTD5/CUL3/Gβγ complex shows that the oligomerization of a substrate receptor can generate a polyvalent E3 ligase complex and that the internal dynamics of the substrate receptor can position a structured target for ubiquitylation in a CRL3 complex. #1: ジャーナル: Proc.Natl.Acad.Sci.USA / 年: 2024 タイトル: Structure and dynamics of a pentameric KCTD5/Cullin3/G beta gamma E3 ubiquitin ligase complex 著者: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / ...著者: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / Mazhab-Jafari, M.T. / Rubinstein, J.L. / Hebert, T.E. / Prive, G.G. #2: ジャーナル: Biorxiv / 年: 2023 タイトル: Structure and dynamics of a pentameric KCTD5/Cullin3/G beta gamma E3 ubiquitin ligase complex 著者: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / ...著者: Nguyen, D.M. / Rath, D.H. / Devost, D. / Petrin, D. / Rizk, R. / Ji, A.X. / Narayanan, N. / Yong, D. / Zhai, A. / Kuntz, D.A. / Mian, M.U.Q. / Pomroy, N.C. / Keszei, A.F.E. / Benlekbir, S. / Mazhab-Jafari, M.T. / Rubinstein, J.L. / Hebert, T.E. / Prive, G.G. | ||||||
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 | 8u83.cif.gz | 805 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8u83.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 8u83.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/u8/8u83 ftp://data.pdbj.org/pub/pdb/validation_reports/u8/8u83 | HTTPS FTP |
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-関連構造データ
関連構造データ | 42004MC 8u7zC 8u80C 8u81C 8u82C 8u84C 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 |
実験データセット #1 | データ参照: 10.5281/zenodo.8341597 / データの種類: other data / 詳細: Zenodo |
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 37416.930 Da / 分子数: 5 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P62873 #2: タンパク質 | 分子量: 44535.152 Da / 分子数: 5 / Fragment: UNP residues 1-381 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CUL3, KIAA0617 / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q13618 #3: タンパク質 | 分子量: 7845.078 Da / 分子数: 5 / Mutation: C68S / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P59768 #4: タンパク質 | 分子量: 26125.562 Da / 分子数: 5 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: KCTD5 / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: Q9NXV2 |
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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: pentameric KCTD5/Cullin3/GBetaGamma E3 ubiquitin ligase complex タイプ: COMPLEX / Entity ID: #4, #2, #1, #3 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: HEK293 |
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 FIELDBright-field microscopy / 倍率(公称値): 75000 X / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 250 nm |
撮影 | 電子線照射量: 49.35 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 実像数: 7464 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.975 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 48895 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
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