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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
Summary
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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