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| Title | A Near-Atomic Structure of the Dark Apoptosome Provides Insight into Assembly and Activation. |
|---|---|
| Journal, issue, pages | Structure, Vol. 25, Issue 1, Page 40-52, Year 2017 |
| Publish date | Jan 3, 2017 |
 Authors | Tat Cheung Cheng / Ildikó V Akey / Shujun Yuan / Zhiheng Yu / Steven J Ludtke / Christopher W Akey /  |
| PubMed Abstract | 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- ...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 β-propellers. We find that the preference for dATP during Dark assembly may be governed by Ser325, which is in close proximity to the 2' carbon of the deoxyribose ring. Interestingly, β-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 β-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. |
 External links | Structure / PubMed:27916517 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.4 Å |
| Structure data | |
| Chemicals |  ChemComp-DTP: |
| Source |
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 Keywords | APOPTOSIS / Dark / apoptosome / apotosis / AAA+ ATPase |
drosophila melanogaster (fruit fly)