- EMDB-36459: cryo-EM structure of the CED-4/CED-3 holoenzyme -
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基本情報
登録情報
データベース: EMDB / ID: EMD-36459
タイトル
cryo-EM structure of the CED-4/CED-3 holoenzyme
マップデータ
試料
複合体: ternary complex of CED-4 with CED-3 CARD and CED-3 catalytic domain
タンパク質・ペプチド: Cell death protein 4
タンパク質・ペプチド: Cell death protein 3
リガンド: MAGNESIUM ION
リガンド: ADENOSINE-5'-TRIPHOSPHATE
キーワード
CED-4 / CED-3 / holoenzyme / APOPTOSIS
機能・相同性
機能・相同性情報
negative regulation of cellular response to manganese ion / positive regulation of cellular response to gamma radiation / Apoptotic cleavage of cellular proteins / Apoptosis induced DNA fragmentation / AKT phosphorylates targets in the cytosol / Signaling by Hippo / Caspase-mediated cleavage of cytoskeletal proteins / Caspase activation via Dependence Receptors in the absence of ligand / Regulation of TNFR1 signaling / Apoptotic cleavage of cell adhesion proteins ...negative regulation of cellular response to manganese ion / positive regulation of cellular response to gamma radiation / Apoptotic cleavage of cellular proteins / Apoptosis induced DNA fragmentation / AKT phosphorylates targets in the cytosol / Signaling by Hippo / Caspase-mediated cleavage of cytoskeletal proteins / Caspase activation via Dependence Receptors in the absence of ligand / Regulation of TNFR1 signaling / Apoptotic cleavage of cell adhesion proteins / positive regulation of egg-laying behavior / BH1 domain binding / regulation of vulval development / positive regulation of apoptotic process involved in development / regulation of development, heterochronic / caspase complex / positive regulation of synapse pruning / peptidase activator activity involved in apoptotic process / caspase-7 / positive regulation of protein processing / regulation of cell fate specification / caspase binding / embryonic morphogenesis / apoptotic process involved in development / negative regulation of execution phase of apoptosis / actin filament depolymerization / programmed cell death / activation of cysteine-type endopeptidase activity / cysteine-type endopeptidase activity involved in execution phase of apoptosis / embryo development ending in birth or egg hatching / execution phase of apoptosis / regulation of locomotion / regulation of cell size / muscle cell cellular homeostasis / regulation of synapse organization / BH3 domain binding / cysteine-type endopeptidase activator activity involved in apoptotic process / protein autoprocessing / endopeptidase activator activity / regulation of cell adhesion / enzyme activator activity / protein catabolic process / regulation of protein stability / ADP binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of neuron apoptotic process / presynapse / perikaryon / nuclear membrane / defense response to Gram-negative bacterium / endopeptidase activity / positive regulation of apoptotic process / cysteine-type endopeptidase activity / neuronal cell body / apoptotic process / negative regulation of apoptotic process / perinuclear region of cytoplasm / magnesium ion binding / protein-containing complex / mitochondrion / proteolysis / ATP binding / identical protein binding / membrane / nucleus / cytoplasm / cytosol 類似検索 - 分子機能
Apoptosis regulator, Ced-4 / Caspase recruitment domain / NB-ARC / NB-ARC domain / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 ...Apoptosis regulator, Ced-4 / Caspase recruitment domain / NB-ARC / NB-ARC domain / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / Peptidase family C14A, His active site / Caspase family histidine active site. / Peptidase C14, caspase non-catalytic subunit p10 / Peptidase family C14A, cysteine active site / Caspase family cysteine active site. / Caspase family p10 domain profile. / Peptidase C14A, caspase catalytic domain / Caspase, interleukin-1 beta converting enzyme (ICE) homologues / Peptidase C14, p20 domain / Caspase family p20 domain profile. / : / Caspase domain / Caspase-like domain superfamily / Death-like domain superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性
Cell death protein 4 / Cell death protein 3 類似検索 - 構成要素
ジャーナル: Life Sci Alliance / 年: 2023 タイトル: Structural insights into CED-3 activation. 著者: Yini Li / Lu Tian / Ying Zhang / Yigong Shi / 要旨: In , onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to ...In , onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to cleave a wide range of substrates, leading to irreversible cell death. Despite decades of investigations, the underlying mechanism of CED-4-facilitated CED-3 activation remains elusive. Here, we report cryo-EM structures of the CED-4 apoptosome and three distinct CED-4/CED-3 complexes that mimic different activation stages for CED-3. In addition to the previously reported octamer in crystal structures, CED-4, alone or in complex with CED-3, exists in multiple oligomeric states. Supported by biochemical analyses, we show that the conserved CARD-CARD interaction promotes CED-3 activation, and initiation of programmed cell death is regulated by the dynamic organization of the CED-4 apoptosome.