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Cell. 2010 Apr 30;141(3):446-57. doi: 10.1016/j.cell.2010.03.017.

Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4.

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  • 1Ministry of Education Protein Science Laboratory, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China.

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.

2010 Elsevier Inc. All rights reserved.

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PMID:
20434985
[PubMed - indexed for MEDLINE]
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