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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

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Published on: March 5, 2018

Structure of an apoptosome-procaspase-9 CARD complex

Shujun Yuan1, Xinchao Yu, Maya Topf

  • 1Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118-2526, USA.

Structure (London, England : 1993)
|May 14, 2010
PubMed

Insights

The apoptosome, crucial for programmed cell death, undergoes conformational changes during activation. This structural study reveals how Apaf-1 assembly enables procaspase-9 activation and explains mutation effects.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Apaf-1 and cytochrome c form the apoptosome, activating procaspase-9 (pc-9) for apoptosis.
  • Understanding apoptosome structure is key to deciphering cell death regulation.

Purpose of the Study:

  • To determine the structure of the apoptosome-pc-9 CARD complex.
  • To elucidate the conformational changes involved in pc-9 activation.

Main Methods:

  • Site-directed thrombinolysis to remove pc-9 catalytic domains.
  • Cryo-electron microscopy to determine the structure at ~9.5 Å resolution.

Main Results:

  • A structural model of the apoptosome-pc-9 CARD complex was generated.
  • Apaf-1 features tandem beta-propellers with docked cytochrome c.
  • Apaf-1 CARDs transition from disordered to ordered upon pc-9 binding, forming a disk structure.

Conclusions:

  • The study reveals conformational changes in Apaf-1 assembly critical for pc-9 activation.
  • The model explains the impact of NOD mutations on the apoptosome's central hub.

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