Three-dimensional Structure of a Double Apoptosome Formed by the Drosophila Apaf-1 Related Killer

The Drosophila Apaf-1 related killer (Dark) forms an apoptosome that activates Dronc, an apical procaspase in the intrinsic cell death pathway. To study this process, we assembled a large Dark complex in the presence of dATP. Remarkably, we found that cytochrome c was not required for assembly and w...

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Bibliographic Details
Published in:Journal of molecular biology 2006-01, Vol.355 (3), p.577-589
Main Authors: Yu, Xinchao, Wang, Lai, Acehan, Devrim, Wang, Xiaodong, Akey, Christopher W.
Format: Article
Language:English
Subjects:
Animals
Apaf-1
Apoptosis
apoptosome
Apoptotic Protease-Activating Factor 1
Cryoelectron Microscopy
Cytochromes c - chemistry
Dark
Drosophila
Drosophila - chemistry
Drosophila Proteins - chemistry
Drosophila Proteins - ultrastructure
Humans
Intracellular Signaling Peptides and Proteins - chemistry
Models, Molecular
Protein Subunits - chemistry
Proteins - chemistry
Proteins - ultrastructure
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Summary:The Drosophila Apaf-1 related killer (Dark) forms an apoptosome that activates Dronc, an apical procaspase in the intrinsic cell death pathway. To study this process, we assembled a large Dark complex in the presence of dATP. Remarkably, we found that cytochrome c was not required for assembly and when added, cytochrome c did not bind to the Dark complex. We then determined a 3D structure of the Dark complex at 18.8 Å resolution using electron cryo-microscopy and single particle methods. In the structure, eight Dark subunits form a wheel-like particle and two of these rings associate face-to-face. In contrast, Apaf-1 forms a single ring that is comprised of seven subunits and each Apaf-1 binds a molecule of cytochrome c. We then used relevant crystal structures to model the Dark complex. This analysis shows that a single Dark ring and the Apaf-1 apoptosome share many key features. When taken together, the data suggest that a single ring in the Dark complex may represent the Drosophila apoptosome. Thus, our analysis provides a domain model of this complex and gives insights into its function.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2005.10.040