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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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    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.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Research Centres and Institutes: Bioinformatics, Bloomsbury Centre for (Closed), Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 27 Jan 2011 14:41
    Last Modified: 02 Aug 2023 16:54
    URI: https://eprints.bbk.ac.uk/id/eprint/2990

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