Structure of an apoptosome-procaspase-9 CARD complex.

Abstract

Apaf-1 coassembles with cytochrome c to form the apoptosome, which then binds and activates procaspase-9 (pc-9). We removed pc-9 catalytic domains from the holoapoptosome by site-directed thrombinolysis. A structure of the resulting apoptosome-pc-9 CARD complex was then determined at approximately 9.5 A resolution. In our model, the central hub is constructed like other AAA+ protein rings but also contains novel features. At higher radius, the regulatory region of each Apaf-1 is comprised of tandem seven and eight blade beta-propellers with cytochrome c docked between them. Remarkably, Apaf-1 CARDs are disordered in the ground state. During activation, each Apaf-1 CARD interacts with a pc-9 CARD and these heterodimers form a flexibly tethered "disk" that sits above the central hub. When taken together, the data reveal conformational changes during Apaf-1 assembly that allow pc-9 activation. The model also provides a plausible explanation for the effects of NOD mutations that have been mapped onto the central hub.

DOI: 10.1016/j.str.2010.04.001
020406020102011201220132014201520162017
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@article{Yuan2010StructureOA, title={Structure of an apoptosome-procaspase-9 CARD complex.}, author={Shujun Yuan and Xinchao Yu and Maya Topf and Steven J. Ludtke and Xiaodong Wang and Christopher W Akey}, journal={Structure}, year={2010}, volume={18 5}, pages={571-83} }