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Structure of the Drosophila Apoptosome at 6.9 Å Resolution

Yuan, Shujun and Yu, Xinchao and Topf, Maya and Dorstyn, Loretta and Kumar, Sharad and Ludtke, Steven J. and Akey, C.W. (2011) Structure of the Drosophila Apoptosome at 6.9 Å Resolution. Structure 19 (1), pp. 128-140. ISSN 09692126.

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Official URL: http://dx.doi.org/10.1016/j.str.2010.10.009

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 not, vert, similar6.9 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.

Item Type: Article
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 27 Jan 2011 14:41
Last Modified: 17 Apr 2013 12:20
URI: http://eprints.bbk.ac.uk/id/eprint/2990

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