Journal
STRUCTURE
Volume 19, Issue 1, Pages 128-140Publisher
CELL PRESS
DOI: 10.1016/j.str.2010.10.009
Keywords
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Funding
- Human Frontier Science Program [RGY0079/2009-C]
- MRC [G0600084]
- National Health and Medical Research Council, Australia
- NIH [R01GM080139, R0GM63834]
- MRC [G0600084] Funding Source: UKRI
- Medical Research Council [G0600084] Funding Source: researchfish
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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 similar to 6.9 angstrom 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.
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