response to G1 DNA damage checkpoint signaling / 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 / positive regulation of cysteine-type endopeptidase activity / Activation of caspases through apoptosome-mediated cleavage / Regulation of the apoptosome activity ...response to G1 DNA damage checkpoint signaling / 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 / positive regulation of cysteine-type endopeptidase activity / Activation of caspases through apoptosome-mediated cleavage / Regulation of the apoptosome activity / SMAC (DIABLO) binds to IAPs / SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes / mitochondrial electron transport, cytochrome c to oxygen / mitochondrial electron transport, ubiquinol to cytochrome c / TP53 Regulates Transcription of Caspase Activators and Caspases / Transcriptional Regulation by E2F6 / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / : / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / forebrain development / cardiac muscle cell apoptotic process / cellular response to transforming growth factor beta stimulus / heat shock protein binding / intrinsic apoptotic signaling pathway / response to nutrient / kidney development / neural tube closure / positive regulation of apoptotic signaling pathway / mitochondrial intermembrane space / ADP binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / nervous system development / regulation of apoptotic process / secretory granule lumen / neuron apoptotic process / ficolin-1-rich granule lumen / electron transfer activity / cell differentiation / response to hypoxia / positive regulation of apoptotic process / nucleotide binding / lipid binding / apoptotic process / heme binding / Neutrophil degranulation / protein-containing complex / extracellular exosome / extracellular region / ATP binding / identical protein binding / nucleus / metal ion binding / cytosol 類似検索 - 分子機能
ジャーナル: Genes Dev / 年: 2015 タイトル: Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. 著者: Mengying Zhou / Yini Li / Qi Hu / Xiao-Chen Bai / Weiyun Huang / Chuangye Yan / Sjors H W Scheres / Yigong Shi / 要旨: The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding ...The apoptotic protease-activating factor 1 (Apaf-1) controls the onset of many known forms of intrinsic apoptosis in mammals. Apaf-1 exists in normal cells as an autoinhibited monomer. Upon binding to cytochrome c and dATP, Apaf-1 oligomerizes into a heptameric complex known as the apoptosome, which recruits and activates cell-killing caspases. Here we present an atomic structure of an intact mammalian apoptosome at 3.8 Å resolution, determined by single-particle, cryo-electron microscopy (cryo-EM). Structural analysis, together with structure-guided biochemical characterization, uncovered how cytochrome c releases the autoinhibition of Apaf-1 through specific interactions with the WD40 repeats. Structural comparison with autoinhibited Apaf-1 revealed how dATP binding triggers a set of conformational changes that results in the formation of the apoptosome. Together, these results constitute the molecular mechanism of cytochrome c- and dATP-mediated activation of Apaf-1.