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https://hdl.handle.net/2440/71781
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Type: | Journal article |
Title: | Structure of the Drosophila apoptosome at 6.9 Å resolution |
Other Titles: | Structure of the Drosophila apoptosome at 6.9 angstrom resolution |
Author: | Yuan, S. Yu, X. Topf, M. Dorstyn, L. Kumar, S. Ludtke, S. Akey, C. |
Citation: | Structure, 2011; 19(1):128-140 |
Publisher: | Cell Press |
Issue Date: | 2011 |
ISSN: | 0969-2126 1878-4186 |
Statement of Responsibility: | Shujun Yuan, Xinchao Yu, Maya Topf, Loretta Dorstyn, Sharad Kumar, Steven J. Ludtke and Christopher W. Akey |
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 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. |
Keywords: | Animals Drosophila melanogaster Caspases Drosophila Proteins Cryoelectron Microscopy Protein Structure, Quaternary Protein Structure, Secondary Protein Structure, Tertiary Structural Homology, Protein Protein Binding Apoptosomes Protein Interaction Domains and Motifs Protein Multimerization |
Rights: | © 2011 Elsevier |
DOI: | 10.1016/j.str.2010.10.009 |
Published version: | http://dx.doi.org/10.1016/j.str.2010.10.009 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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