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-Structure paper
Title | Atomic structure of the apoptosome: mechanism of cytochrome c- and dATP-mediated activation of Apaf-1. |
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Journal, issue, pages | Genes Dev, Vol. 29, Issue 22, Page 2349-2361, Year 2015 |
Publish date | Nov 15, 2015 |
![]() | Mengying Zhou / Yini Li / Qi Hu / Xiao-Chen Bai / Weiyun Huang / Chuangye Yan / Sjors H W Scheres / Yigong Shi / ![]() ![]() |
PubMed Abstract | 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. |
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Methods | EM (single particle) |
Resolution | 3.8 - 4.4 Å |
Structure data | |
Chemicals | ![]() ChemComp-DTP: ![]() ChemComp-MG: ![]() ChemComp-HEM: |
Source |
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![]() | APOPTOSIS / Apoptosome / cryo-EM structure / Apaf-1 |