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基本情報
登録情報 | データベース: EMDB / ID: EMD-4025 | |||||||||
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タイトル | Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion mutant bound to the E2 UBE2C (aka UBCH10) poised for ubiquitin ligation to substrate. | |||||||||
![]() | Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion mutant bound to the E2 UBE2C (aka UBCH10) poised for ubiquitin ligation to substrate | |||||||||
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機能・相同性 | ![]() protein localization to septin ring / mitotic morphogenesis checkpoint signaling / metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / cellular bud neck septin ring / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / free ubiquitin chain polymerization ...protein localization to septin ring / mitotic morphogenesis checkpoint signaling / metaphase/anaphase transition of cell cycle / metaphase/anaphase transition of meiosis I / cellular bud neck septin ring / Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components / mitotic checkpoint complex / positive regulation of anaphase-promoting complex-dependent catabolic process / positive regulation of exit from mitosis / free ubiquitin chain polymerization / regulation of meiotic nuclear division / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / positive regulation of synapse maturation / Inactivation of APC/C via direct inhibition of the APC/C complex / APC/C:Cdc20 mediated degradation of mitotic proteins / Phosphorylation of Emi1 / anaphase-promoting complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of meiotic cell cycle / metaphase/anaphase transition of mitotic cell cycle / anaphase-promoting complex-dependent catabolic process / (E3-independent) E2 ubiquitin-conjugating enzyme / positive regulation of synaptic plasticity / regulation of exit from mitosis / Phosphorylation of the APC/C / anaphase-promoting complex binding / cellular bud neck / ubiquitin ligase activator activity / positive regulation of mitotic metaphase/anaphase transition / positive regulation of ubiquitin protein ligase activity / protein K11-linked ubiquitination / enzyme-substrate adaptor activity / regulation of mitotic metaphase/anaphase transition / positive regulation of dendrite morphogenesis / exit from mitosis / ubiquitin-ubiquitin ligase activity / mitotic sister chromatid cohesion / mitotic metaphase chromosome alignment / E2 ubiquitin-conjugating enzyme / mitotic spindle assembly checkpoint signaling / ubiquitin-like protein ligase binding / ubiquitin conjugating enzyme activity / Regulation of APC/C activators between G1/S and early anaphase / cullin family protein binding / ubiquitin-like ligase-substrate adaptor activity / Transcriptional Regulation by VENTX / mitotic spindle assembly / positive regulation of axon extension / protein K48-linked ubiquitination / heterochromatin / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / ubiquitin ligase complex / Resolution of Sister Chromatid Cohesion / APC/C:Cdc20 mediated degradation of Cyclin B / regulation of mitotic cell cycle / APC-Cdc20 mediated degradation of Nek2A / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / nuclear periphery / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / Assembly of the pre-replicative complex / RHO GTPases Activate Formins / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / protein catabolic process / brain development / mitotic spindle / CDK-mediated phosphorylation and removal of Cdc6 / kinetochore / spindle pole / spindle / protein polyubiquitination / Separation of Sister Chromatids / ubiquitin-protein transferase activity / G2/M transition of mitotic cell cycle / microtubule cytoskeleton / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / nervous system development / mitotic cell cycle / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / cell differentiation / non-specific serine/threonine protein kinase / Ub-specific processing proteases / regulation of cell cycle / protein kinase activity / protein ubiquitination / cell cycle / phosphorylation / cell division / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / centrosome 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 6.1 Å | |||||||||
![]() | Stark H / Schulman BA / Peters JM | |||||||||
![]() | ![]() タイトル: Cryo-EM of Mitotic Checkpoint Complex-Bound APC/C Reveals Reciprocal and Conformational Regulation of Ubiquitin Ligation. 著者: Masaya Yamaguchi / Ryan VanderLinden / Florian Weissmann / Renping Qiao / Prakash Dube / Nicholas G Brown / David Haselbach / Wei Zhang / Sachdev S Sidhu / Jan-Michael Peters / Holger Stark / ...著者: Masaya Yamaguchi / Ryan VanderLinden / Florian Weissmann / Renping Qiao / Prakash Dube / Nicholas G Brown / David Haselbach / Wei Zhang / Sachdev S Sidhu / Jan-Michael Peters / Holger Stark / Brenda A Schulman / ![]() ![]() ![]() ![]() 要旨: The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). ...The mitotic checkpoint complex (MCC) coordinates proper chromosome biorientation on the spindle with ubiquitination activities of CDC20-activated anaphase-promoting complex/cyclosome (APC/C(CDC20)). APC/C(CDC20) and two E2s, UBE2C and UBE2S, catalyze ubiquitination through distinct architectures for linking ubiquitin (UB) to substrates and elongating polyUB chains, respectively. MCC, which contains a second molecule of CDC20, blocks APC/C(CDC20)-UBE2C-dependent ubiquitination of Securin and Cyclins, while differentially determining or inhibiting CDC20 ubiquitination to regulate spindle surveillance, checkpoint activation, and checkpoint termination. Here electron microscopy reveals conformational variation of APC/C(CDC20)-MCC underlying this multifaceted regulation. MCC binds APC/C-bound CDC20 to inhibit substrate access. However, rotation about the CDC20-MCC assembly and conformational variability of APC/C modulate UBE2C-catalyzed ubiquitination of MCC's CDC20 molecule. Access of UBE2C is limiting for subsequent polyubiquitination by UBE2S. We propose that conformational dynamics of APC/C(CDC20)-MCC modulate E2 activation and determine distinctive ubiquitination activities as part of a response mechanism ensuring accurate sister chromatid segregation. | |||||||||
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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画像 | ![]() | 159.1 KB | ||
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文書・要旨 | ![]() | 343.7 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 343.3 KB | 表示 | |
XML形式データ | ![]() | 6 KB | 表示 | |
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「今月の分子」の関連する項目 |
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注釈 | Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion mutant bound to the E2 UBE2C (aka UBCH10) poised for ubiquitin ligation to substrate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.57 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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試料の構成要素
-全体 : Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion...
全体 | 名称: Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion mutant bound to the E2 UBE2C (aka UBCH10) poised for ubiquitin ligation to substrate. |
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要素 |
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-超分子 #1: Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion...
超分子 | 名称: Human Anaphase-promoting complex/Cyclosome (APC/C) APC15 deletion mutant bound to the E2 UBE2C (aka UBCH10) poised for ubiquitin ligation to substrate. タイプ: complex / ID: 1 / 親要素: 0 |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
分子量 | 理論値: 1.5 MDa |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.1 mg/mL | ||||||||||||
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緩衝液 | pH: 8 構成要素:
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV | ||||||||||||
詳細 | Grafix treated complex |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 検出モード: INTEGRATING / 撮影したグリッド数: 1 / 実像数: 1476 / 平均露光時間: 1.0 sec. / 平均電子線量: 40.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 最大 デフォーカス(補正後): 0.0035 µm / 最小 デフォーカス(補正後): 0.0007 µm / 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD / Cs: 0.001 mm / 倍率(公称値): 94000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |