+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-6690 | |||||||||
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タイトル | Apaf-1-Caspase-9 holoenzyme | |||||||||
マップデータ | Apaf-1-Caspase-9 holoenzyme platform | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 caspase-9 / response to G1 DNA damage checkpoint signaling / caspase complex / cytochrome c-heme linkage / Formation of apoptosome / regulation of apoptotic DNA fragmentation / apoptosome / cytochrome complex / activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / leukocyte apoptotic process ...caspase-9 / response to G1 DNA damage checkpoint signaling / caspase complex / cytochrome c-heme linkage / Formation of apoptosome / regulation of apoptotic DNA fragmentation / apoptosome / cytochrome complex / activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / leukocyte apoptotic process / glial cell apoptotic process / response to cobalt ion / cysteine-type endopeptidase activity involved in apoptotic signaling pathway / positive regulation of cysteine-type endopeptidase activity / Caspase activation via Dependence Receptors in the absence of ligand / Activation of caspases through apoptosome-mediated cleavage / Regulation of the apoptosome activity / cysteine-type endopeptidase activity involved in apoptotic process / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / AKT phosphorylates targets in the cytosol / mitochondrial electron transport, cytochrome c to oxygen / fibroblast apoptotic process / epithelial cell apoptotic process / platelet formation / mitochondrial electron transport, ubiquinol to cytochrome c / TP53 Regulates Transcription of Caspase Activators and Caspases / Transcriptional Regulation by E2F6 / Constitutive Signaling by AKT1 E17K in Cancer / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / protein maturation / : / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / signal transduction in response to DNA damage / forebrain development / cardiac muscle cell apoptotic process / enzyme activator activity / cellular response to transforming growth factor beta stimulus / heat shock protein binding / intrinsic apoptotic signaling pathway / cellular response to dexamethasone stimulus / response to nutrient / kidney development / neural tube closure / response to ischemia / positive regulation of apoptotic signaling pathway / NOD1/2 Signaling Pathway / mitochondrial intermembrane space / protein processing / ADP binding / SH3 domain binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / intrinsic apoptotic signaling pathway in response to DNA damage / cellular response to UV / positive regulation of neuron apoptotic process / response to estradiol / nervous system development / peptidase activity / regulation of apoptotic process / secretory granule lumen / neuron apoptotic process / ficolin-1-rich granule lumen / response to lipopolysaccharide / electron transfer activity / cell differentiation / response to hypoxia / positive regulation of apoptotic process / cysteine-type endopeptidase activity / nucleotide binding / lipid binding / apoptotic process / DNA damage response / heme binding / Neutrophil degranulation / protein kinase binding / protein-containing complex / mitochondrion / proteolysis / extracellular exosome / extracellular region / ATP binding / identical protein binding / nucleus / metal ion binding / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Equus caballus (ウマ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.4 Å | |||||||||
データ登録者 | Li Y / Zhou M / Hu Q / Shi Y | |||||||||
引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2017 タイトル: Mechanistic insights into caspase-9 activation by the structure of the apoptosome holoenzyme. 著者: Yini Li / Mengying Zhou / Qi Hu / Xiao-Chen Bai / Weiyun Huang / Sjors H W Scheres / Yigong Shi / 要旨: Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is ...Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is indispensable for caspase-9 activation by together forming a holoenzyme. The molecular mechanism of caspase-9 activation remains largely enigmatic. Here, we report the cryoelectron microscopy (cryo-EM) structure of an apoptotic holoenzyme and structure-guided biochemical analyses. The caspase recruitment domains (CARDs) of Apaf-1 and caspase-9 assemble in two different ways: a 4:4 complex docks onto the central hub of the apoptosome, and a 2:1 complex binds the periphery of the central hub. The interface between the CARD complex and the central hub is required for caspase-9 activation within the holoenzyme. Unexpectedly, the CARD of free caspase-9 strongly inhibits its proteolytic activity. These structural and biochemical findings demonstrate that the apoptosome activates caspase-9 at least in part through sequestration of the inhibitory CARD domain. | |||||||||
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_6690.map.gz | 117 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-6690-v30.xml emd-6690.xml | 16.4 KB 16.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_6690.png | 94.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-6690 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6690 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_6690_validation.pdf.gz | 483.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_6690_full_validation.pdf.gz | 483 KB | 表示 | |
XML形式データ | emd_6690_validation.xml.gz | 6.5 KB | 表示 | |
CIF形式データ | emd_6690_validation.cif.gz | 7.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6690 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-6690 | 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_6690.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Apaf-1-Caspase-9 holoenzyme platform | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.34 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
-試料の構成要素
+全体 : Apaf-1 apoptosome
+超分子 #1: Apaf-1 apoptosome
+超分子 #2: Apaf-1
+超分子 #3: cytochrome c
+超分子 #4: Apaf-1 CARD
+超分子 #5: caspase-9 CARD
+分子 #1: Apoptotic protease-activating factor 1
+分子 #2: Cytochrome c
+分子 #3: Apoptotic protease-activating factor 1
+分子 #4: Caspase
+分子 #5: 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE
+分子 #6: MAGNESIUM ION
+分子 #7: PROTOPORPHYRIN IX CONTAINING FE
-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: 7.5 |
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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 II (4k x 4k) 平均電子線量: 32.0 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
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 240130 |
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初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |