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基本情報
登録情報 | データベース: PDB / ID: 9ivd | ||||||||||||||||||||||||
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タイトル | Cryo-EM structure of CyclinD1 bound AMBRA1-DDB1 | ||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN / E3 ligase | ||||||||||||||||||||||||
機能・相同性 | ![]() positive regulation of free ubiquitin chain polymerization / cyclin D1-CDK4 complex / cyclin D1-CDK6 complex / re-entry into mitotic cell cycle / Drug-mediated inhibition of CDK4/CDK6 activity / RUNX3 regulates WNT signaling / response to mitochondrial depolarisation / response to leptin / positive regulation of mitophagy / positive regulation of mammary gland epithelial cell proliferation ...positive regulation of free ubiquitin chain polymerization / cyclin D1-CDK4 complex / cyclin D1-CDK6 complex / re-entry into mitotic cell cycle / Drug-mediated inhibition of CDK4/CDK6 activity / RUNX3 regulates WNT signaling / response to mitochondrial depolarisation / response to leptin / positive regulation of mitophagy / positive regulation of mammary gland epithelial cell proliferation / Transcriptional regulation by RUNX2 / positive regulation of cyclin-dependent protein serine/threonine kinase activity / positive regulation by virus of viral protein levels in host cell / spindle assembly involved in female meiosis / epigenetic programming in the zygotic pronuclei / Cul4-RING E3 ubiquitin ligase complex / cyclin-dependent protein serine/threonine kinase activator activity / proline-rich region binding / UV-damage excision repair / Regulation of RUNX1 Expression and Activity / neural tube development / positive regulation of regulatory T cell differentiation / biological process involved in interaction with symbiont / cyclin-dependent protein serine/threonine kinase regulator activity / regulation of mitotic cell cycle phase transition / mammary gland epithelial cell proliferation / WD40-repeat domain binding / negative regulation of cardiac muscle cell apoptotic process / response to UV-A / Cul4A-RING E3 ubiquitin ligase complex / negative regulation of epithelial cell differentiation / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / Macroautophagy / PTK6 Regulates Cell Cycle / negative regulation of reproductive process / negative regulation of developmental process / fat cell differentiation / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / microtubule organizing center / regulation of G1/S transition of mitotic cell cycle / cullin family protein binding / viral release from host cell / protein phosphatase activator activity / RUNX3 regulates p14-ARF / Transcriptional Regulation by VENTX / axoneme / autophagosome assembly / mammary gland alveolus development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / bicellular tight junction / positive regulation of G1/S transition of mitotic cell cycle / ectopic germ cell programmed cell death / ubiquitin-like ligase-substrate adaptor activity / positive regulation of viral genome replication / Regulation of MITF-M-dependent genes involved in cell cycle and proliferation / proteasomal protein catabolic process / endoplasmic reticulum unfolded protein response / cyclin-dependent protein kinase holoenzyme complex / mitophagy / lactation / phagocytic vesicle / mitotic G1 DNA damage checkpoint signaling / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of autophagy / transcription repressor complex / positive regulation of gluconeogenesis / autophagosome / liver regeneration / cellular response to starvation / Ubiquitin-dependent degradation of Cyclin D / nucleotide-excision repair / Recognition of DNA damage by PCNA-containing replication complex / regulation of circadian rhythm / DNA Damage Recognition in GG-NER / Pre-NOTCH Transcription and Translation / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / SCF(Skp2)-mediated degradation of p27/p21 / G1/S transition of mitotic cell cycle / RMTs methylate histone arginines / Formation of Incision Complex in GG-NER / histone deacetylase binding / Wnt signaling pathway / neuron differentiation / Dual incision in TC-NER / protein polyubiquitination / positive regulation of protein catabolic process / Gap-filling DNA repair synthesis and ligation in TC-NER / Cyclin D associated events in G1 / transcription corepressor activity / cellular response to UV / rhythmic process / positive regulation of protein phosphorylation / site of double-strand break / Neddylation / GTPase binding / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity 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: 3.55 Å | ||||||||||||||||||||||||
![]() | Wang, Y. / Liu, M. / Su, M.-Y. / Stjepanovic, G. | ||||||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Mechanism of D-type cyclin recognition by the AMBRA1 E3 ligase receptor. 著者: Yang Wang / Ming Liu / Shan Wang / Xinyi Mai / Xi Wang / Fei Teng / Tianrui Lyu / Ming-Yuan Su / Goran Stjepanovic / ![]() 要旨: AMBRA1 is a tumor suppressor protein that functions as a substrate receptor in the ubiquitin conjugation system and regulates the stability of D-type cyclins and cell proliferation. Here, we present ...AMBRA1 is a tumor suppressor protein that functions as a substrate receptor in the ubiquitin conjugation system and regulates the stability of D-type cyclins and cell proliferation. Here, we present the cryo-EM structure of cyclin D1-bound AMBRA1-DDB1 complex at 3.55-Å resolution. The structure reveals a substrate interaction surface on the AMBRA1 WD40 domain that specifically binds to the C-terminal region of D-type cyclins. This interaction is dependent on the phosphorylation of Thr residue in the C-terminal phosphodegron site of D-type cyclins. The phosphodegron motif folds into a turn-like conformation, followed by a 3 helix that promotes its assembly with AMBRA1. In addition, we show that AMBRA1 mutants, which are defective in cyclin D1 binding, lead to cyclin D1 accumulation and DNA damage. Understanding the AMBRA1-D-type cyclin structure enhances the knowledge of the molecular mechanisms that govern the cell cycle control and may lead to potential therapeutic approaches for cancers linked to abnormal cyclin D activity. | ||||||||||||||||||||||||
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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 | ![]() | 226.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 164.3 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 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1 MB | 表示 | |
XML形式データ | ![]() | 40.7 KB | 表示 | |
CIF形式データ | ![]() | 62 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 60925MC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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
#1: タンパク質 | 分子量: 33847.090 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
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#2: タンパク質 | 分子量: 44496.871 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
#3: タンパク質 | 分子量: 127097.469 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() |
研究の焦点であるリガンドがあるか | Y |
Has protein modification | 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 |
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試料調製
構成要素 | 名称: Complex of AMBRA1-DDB1 bound to CyclinD1-CDK4 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.244 MDa / 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.4 |
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 |
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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 / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 1.198 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.55 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1015935 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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