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, 141 (3), 446-57

Crystal Structure of the Caenorhabditis Elegans Apoptosome Reveals an Octameric Assembly of CED-4

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Crystal Structure of the Caenorhabditis Elegans Apoptosome Reveals an Octameric Assembly of CED-4

Shiqian Qi et al. Cell.

Abstract

The CED-4 homo-oligomer or apoptosome is required for initiation of programmed cell death in Caenorhabditis elegans by facilitating autocatalytic activation of the CED-3 caspase zymogen. How the CED-4 apoptosome assembles and activates CED-3 remains enigmatic. Here we report the crystal structure of the complete CED-4 apoptosome and show that it consists of eight CED-4 molecules, organized as a tetramer of an asymmetric dimer via a previously unreported interface among AAA(+) ATPases. These eight CED-4 molecules form a funnel-shaped structure. The mature CED-3 protease is monomeric in solution and forms an active holoenzyme with the CED-4 apoptosome, within which the protease activity of CED-3 is markedly stimulated. Unexpectedly, the octameric CED-4 apoptosome appears to bind only two, not eight, molecules of mature CED-3. The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA(+) ATPases and suggests a mechanism for the activation of CED-3.

Comment in

  • The Apoptosome at High Resolution
    X Teng et al. Cell 141 (3), 402-4. PMID 20434981.
    The mechanism by which the apoptosome activates caspases during apoptosis has been controversial. Qi et al. (2010) now present a crystal structure of a funnel-shaped octa …

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