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Title | Structure of the Drosophila apoptosome at 6.9 å resolution. |
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Journal, issue, pages | Structure, Vol. 19, Issue 1, Page 128-140, Year 2011 |
Publish date | Jan 12, 2011 |
Authors | Shujun Yuan / Xinchao Yu / Maya Topf / Loretta Dorstyn / Sharad Kumar / Steven J Ludtke / Christopher W Akey / |
PubMed Abstract | The Drosophila Apaf-1 related killer forms an apoptosome in the intrinsic cell death pathway. In this study we show that Dark forms a single ring when initiator procaspases are bound. This Dark-Dronc ...The Drosophila Apaf-1 related killer forms an apoptosome in the intrinsic cell death pathway. In this study we show that Dark forms a single ring when initiator procaspases are bound. This Dark-Dronc complex cleaves DrICE efficiently; hence, a single ring represents the Drosophila apoptosome. We then determined the 3D structure of a double ring at ∼6.9 Å resolution and created a model of the apoptosome. Subunit interactions in the Dark complex are similar to those in Apaf-1 and CED-4 apoptosomes, but there are significant differences. In particular, Dark has "lost" a loop in the nucleotide-binding pocket, which opens a path for possible dATP exchange in the apoptosome. In addition, caspase recruitment domains (CARDs) form a crown on the central hub of the Dark apoptosome. This CARD geometry suggests that conformational changes will be required to form active Dark-Dronc complexes. When taken together, these data provide insights into apoptosome structure, function, and evolution. |
External links | Structure / PubMed:21220123 / PubMed Central |
Methods | EM (single particle) |
Resolution | 6.9 Å |
Structure data | |
Chemicals | ChemComp-MG: ChemComp-DTP: |
Source |
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Keywords | APOPTOSIS / Drosophila apoptosome / programmed cell death |