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      Structure of an Apoptosome-Procaspase-9 CARD Complex

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      Structure
      Elsevier BV

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          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. Copyright 2010 Elsevier Ltd. All rights reserved.

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          Author and article information

          Journal
          Structure
          Structure
          Elsevier BV
          09692126
          May 2010
          May 2010
          : 18
          : 5
          : 571-583
          Article
          10.1016/j.str.2010.04.001
          2874686
          20462491
          4f89bfee-85f4-46a6-a8f6-093333089921
          © 2010

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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