+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-6691 | |||||||||
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タイトル | Apaf-1-Caspase-9 holoenzyme | |||||||||
マップデータ | None | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 カスパーゼ-9 / response to G1 DNA damage checkpoint signaling / caspase complex / cytochrome c-heme linkage / regulation of apoptotic DNA fragmentation / Formation of apoptosome / アポトソーム / cytochrome complex / activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / leukocyte apoptotic process ...カスパーゼ-9 / response to G1 DNA damage checkpoint signaling / caspase complex / cytochrome c-heme linkage / regulation of apoptotic DNA fragmentation / Formation of apoptosome / アポトソーム / 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 / Regulation of the apoptosome activity / Activation of caspases through apoptosome-mediated cleavage / cysteine-type endopeptidase activity involved in apoptotic process / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / mitochondrial electron transport, cytochrome c to oxygen / fibroblast apoptotic process / AKT phosphorylates targets in the cytosol / epithelial cell apoptotic process / mitochondrial electron transport, ubiquinol to cytochrome c / platelet formation / 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 / enzyme activator activity / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / respirasome / signal transduction in response to DNA damage / forebrain development / positive regulation of apoptotic signaling pathway / cardiac muscle cell apoptotic process / cellular response to transforming growth factor beta stimulus / heat shock protein binding / cellular response to dexamethasone stimulus / intrinsic apoptotic signaling pathway / response to nutrient / kidney development / neural tube closure / response to ischemia / ADP binding / NOD1/2 Signaling Pathway / ミトコンドリア / protein processing / SH3 domain binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of neuron apoptotic process / cellular response to UV / intrinsic apoptotic signaling pathway in response to DNA damage / response to estradiol / nervous system development / peptidase activity / neuron apoptotic process / regulation of apoptotic process / secretory granule lumen / ficolin-1-rich granule lumen / response to lipopolysaccharide / 細胞分化 / electron transfer activity / 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 / ミトコンドリア / タンパク質分解 / extracellular exosome / extracellular region / ATP binding / identical protein binding / metal ion binding / 細胞核 / 細胞質基質 / 細胞質 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: 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_6691.map.gz | 12.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-6691-v30.xml emd-6691.xml | 9 KB 9 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_6691.png | 72.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-6691 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-6691 | 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_6691.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 | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
全体 | 名称: Apaf-1 apoptosome |
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要素 |
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-超分子 #1: Apaf-1 apoptosome
超分子 | 名称: Apaf-1 apoptosome / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#7 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Insect cell expression vector pTIE1 (その他) / 組換プラスミド: pFasBac |
-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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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 FIELDBright-field microscopy |
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 |
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
-画像解析
初期 角度割当 | タイプ: PROJECTION MATCHING |
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最終 角度割当 | タイプ: PROJECTION MATCHING |
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 |