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

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Apoptosome structure, assembly, and procaspase activation

Shujun Yuan1, Christopher W Akey

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

Structure (London, England : 1993)
|April 9, 2013
PubMed

Insights

The apoptosome, a cell death platform, activates procaspases via CARD-CARD disk assembly. This mechanism enhances local procaspase-9 concentration, facilitating intrinsic cell death pathway activation.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death

Background:

  • Apaf-1-like molecules form the apoptosome, a crucial platform for initiating programmed cell death.
  • The intrinsic cell death pathway relies on apoptosome-mediated activation of procaspases.

Purpose of the Study:

  • To elucidate the structural assembly of cell death platforms, specifically the apoptosome.
  • To understand the molecular interactions driving procaspase activation within the apoptosome.

Main Methods:

  • Integration of crystal structures of Apaf-1 monomers and CED-4 dimers.
  • Analysis of existing apoptosome structures across different species (humans, nematodes, flies).

Main Results:

  • Identified the formation of a CARD-CARD disk between procaspase-9 and Apaf-1 in humans.
  • Demonstrated that this disk interacts with the apoptosome platform, creating an asymmetric proteolysis machine.
  • Revealed that the disk concentrates procaspase-9 catalytic domains, promoting zymogen activation.

Conclusions:

  • The CARD-CARD disk is essential for efficient procaspase-9 activation on the apoptosome.
  • This structural insight provides a foundation for future research into apoptosome-mediated cell death.
  • Comparative structural analysis highlights conserved mechanisms in cell death platform assembly.

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