Journal
STRUCTURE
Volume 25, Issue 1, Pages 40-52Publisher
CELL PRESS
DOI: 10.1016/j.str.2016.11.002
Keywords
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Funding
- NIH [R01 GM080139, R01 GM63834]
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In Drosophila, the Apaf-1-related killer (Dark) forms an apoptosome that activates procaspases. To investigate function, we have determined a near-atomic structure of Dark double rings using cryo-electron microscopy. We then built a nearly complete model of the apoptosome that includes 7- and 8-blade beta-propellers. We find that the preference for dATP during Dark assembly may be governed by Ser325, which is in close proximity to the 20 carbon of the deoxyribose ring. Interestingly, beta-propellers in V-shaped domains of the Dark apoptosome are more widely separated, relative to these features in the Apaf-1 apoptosome. This wider spacing may be responsible for the lack of cytochrome c binding to beta-propellers in the Dark apoptosome. Our structure also highlights the roles of two loss-of-function mutations that may block Dark assembly. Finally, the improved model provides a framework to understand apical procaspase activation in the intrinsic cell death pathway.
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