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.
全体 : Heptameric apoptosome of activated human Apaf-1 binding to horse ...
全体
名称: Heptameric apoptosome of activated human Apaf-1 binding to horse cytochrome c and dATP
要素
試料: Heptameric apoptosome of activated human Apaf-1 binding to horse cytochrome c and dATP
タンパク質・ペプチド: The apoptotic protease activating factor 1
タンパク質・ペプチド: cytochrome c
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超分子 #1000: Heptameric apoptosome of activated human Apaf-1 binding to horse ...
超分子
名称: Heptameric apoptosome of activated human Apaf-1 binding to horse cytochrome c and dATP タイプ: sample / ID: 1000 / 集合状態: Heptamer / Number unique components: 2