+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-10516 | |||||||||
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タイトル | Cryo-EM structure of the Anaphase-promoting complex/Cyclosome, in complex with the Mitotic checkpoint complex (APC/C-MCC) at 3.8 angstrom resolution | |||||||||
マップデータ | Overall map | |||||||||
試料 |
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キーワード | E3 ligase / Complex / Mitotic checkpoint complex / CELL CYCLE | |||||||||
機能・相同性 | 機能・相同性情報 metaphase/anaphase transition of cell cycle / mitotic spindle assembly checkpoint MAD1-MAD2 complex / metaphase/anaphase transition of meiosis I / 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 mitotic cell cycle spindle assembly checkpoint / regulation of meiotic nuclear division / establishment of centrosome localization / meiotic sister chromatid cohesion, centromeric ...metaphase/anaphase transition of cell cycle / mitotic spindle assembly checkpoint MAD1-MAD2 complex / metaphase/anaphase transition of meiosis I / 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 mitotic cell cycle spindle assembly checkpoint / regulation of meiotic nuclear division / establishment of centrosome localization / meiotic sister chromatid cohesion, centromeric / positive regulation of synapse maturation / Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase / regulation of mitotic cell cycle spindle assembly checkpoint / protein branched polyubiquitination / 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 / anaphase-promoting complex-dependent catabolic process / metaphase/anaphase transition of mitotic cell cycle / positive regulation of synaptic plasticity / regulation of exit from mitosis / anaphase-promoting complex binding / Phosphorylation of the APC/C / nuclear pore nuclear basket / outer kinetochore / protein localization to chromosome, centromeric region / positive regulation of mitotic metaphase/anaphase transition / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / protein K11-linked ubiquitination / enzyme-substrate adaptor activity / positive regulation of dendrite morphogenesis / regulation of mitotic metaphase/anaphase transition / ubiquitin-ubiquitin ligase activity / negative regulation of ubiquitin protein ligase activity / mitotic sister chromatid cohesion / mitotic metaphase chromosome alignment / mitotic spindle assembly checkpoint signaling / establishment of mitotic spindle orientation / Regulation of APC/C activators between G1/S and early anaphase / mitotic sister chromatid segregation / cullin family protein binding / Transcriptional Regulation by VENTX / negative regulation of mitotic cell cycle / mitotic spindle assembly / ubiquitin-like ligase-substrate adaptor activity / 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 / regulation of mitotic cell cycle / Resolution of Sister Chromatid Cohesion / APC/C:Cdc20 mediated degradation of Cyclin B / APC-Cdc20 mediated degradation of Nek2A / 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 / brain development / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / negative regulation of protein catabolic process / CDK-mediated phosphorylation and removal of Cdc6 / mitotic spindle / kinetochore / spindle pole / spindle / ubiquitin-protein transferase activity / Separation of Sister Chromatids / microtubule cytoskeleton / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / mitotic cell cycle / nervous system development / Senescence-Associated Secretory Phenotype (SASP) / ubiquitin-dependent protein catabolic process / protein phosphatase binding / molecular adaptor activity / cell differentiation / non-specific serine/threonine protein kinase / protein kinase activity / Ub-specific processing proteases / protein ubiquitination / cell division / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / ubiquitin protein ligase binding / negative regulation of apoptotic process / nucleolus / apoptotic process / perinuclear region of cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | |||||||||
データ登録者 | Alfieri C / Barford D | |||||||||
資金援助 | 英国, 1件
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引用 | ジャーナル: EMBO Rep / 年: 2020 タイトル: A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase. 著者: Claudio Alfieri / Thomas Tischer / David Barford / 要旨: The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of ...The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is restrained by the spindle assembly checkpoint (SAC), which coordinates chromosome segregation with the assembly of the mitotic spindle. The SAC effector is the mitotic checkpoint complex (MCC), which binds and inhibits the APC/C. It is incompletely understood how the APC/C switches substrate specificity in a cell cycle-specific manner. For instance, it is unclear how in prometaphase, when APC/C activity towards cyclin B and securin is repressed by the MCC, the kinase Nek2A is ubiquitinated. Here, we combine biochemical and structural analysis with functional studies in cells to show that Nek2A is a conformational-specific binder of the APC/C-MCC complex (APC/C ) and that, in contrast to cyclin A, Nek2A can be ubiquitinated efficiently by the APC/C in conjunction with both the E2 enzymes UbcH10 and UbcH5. We propose that these special features of Nek2A allow its prometaphase-specific ubiquitination. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_10516.map.gz | 8.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-10516-v30.xml emd-10516.xml | 42.1 KB 42.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_10516.png | 70.3 KB | ||
Filedesc metadata | emd-10516.cif.gz | 12.1 KB | ||
その他 | emd_10516_additional_1.map.gz emd_10516_additional_2.map.gz emd_10516_additional_3.map.gz | 6 MB 7.1 MB 6.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-10516 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10516 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_10516_validation.pdf.gz | 429.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_10516_full_validation.pdf.gz | 428.7 KB | 表示 | |
XML形式データ | emd_10516_validation.xml.gz | 6.3 KB | 表示 | |
CIF形式データ | emd_10516_validation.cif.gz | 7.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10516 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10516 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_10516.map.gz / 形式: CCP4 / 大きさ: 70.2 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Overall map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.36 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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-添付データ
-追加マップ: Platform body
ファイル | emd_10516_additional_1.map | ||||||||||||
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注釈 | Platform body | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: TPRlobe body
ファイル | emd_10516_additional_2.map | ||||||||||||
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注釈 | TPRlobe body | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: PC repeats cdc20 and mcc body
ファイル | emd_10516_additional_3.map | ||||||||||||
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注釈 | PC repeats cdc20 and mcc body | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Anaphase-promoting complex/Cyclosome, in complex with the Mitotic...
+超分子 #1: Anaphase-promoting complex/Cyclosome, in complex with the Mitotic...
+分子 #1: Anaphase-promoting complex subunit 1
+分子 #2: Anaphase-promoting complex subunit 11
+分子 #3: Cell division cycle protein 23 homolog
+分子 #4: Anaphase-promoting complex subunit 15
+分子 #5: Anaphase-promoting complex subunit 16
+分子 #6: Cell division cycle protein 27 homolog
+分子 #7: Anaphase-promoting complex subunit CDC26
+分子 #8: Anaphase-promoting complex subunit 4
+分子 #9: Cell division cycle protein 16 homolog
+分子 #10: Anaphase-promoting complex subunit 10
+分子 #11: Anaphase-promoting complex subunit 13
+分子 #12: Anaphase-promoting complex subunit 2
+分子 #13: Anaphase-promoting complex subunit 5
+分子 #14: Cell division cycle protein 20 homolog
+分子 #15: Cell division cycle protein 20 homolog
+分子 #16: Mitotic checkpoint serine/threonine-protein kinase BUB1 beta
+分子 #17: Anaphase-promoting complex subunit 7
+分子 #18: Mitotic spindle assembly checkpoint protein MAD2A
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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撮影 | フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 平均電子線量: 27.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 343551 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |