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

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.

• Authors: Shiqian Qi, Yuxuan Pang, Qi Hu, Qun Liu, Hua Li, Yulian Zhou, Tianxi He, Qionglin Liang, Yexing Liu, Xiaoqiu Yuan, Guoan Luo, Huilin Li, Jiawei Wang, Nieng Yan, Yigong Shi
• Journal: Cell (Cell) Vol. 141 Issue 3 Pg. 446-57 (Apr 30 2010) ISSN: 1097-4172 [Electronic] United States
• PMID: 20434985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• Apoptosomes
• Apoptotic Protease-Activating Factor 1
• Caenorhabditis elegans Proteins
• Calcium-Binding Proteins
• Ced-4 protein, C elegans
• Caspases
• ced-3 protein, C elegans

Topics

• Amino Acid Sequence
• Animals
• Apoptosomes (metabolism)
• Apoptotic Protease-Activating Factor 1 (metabolism)
• Caenorhabditis elegans (chemistry, metabolism)
• Caenorhabditis elegans Proteins (chemistry)
• Calcium-Binding Proteins (chemistry)
• Caspases (chemistry)
• Crystallography, X-Ray
• Models, Molecular
• Sequence Alignment
• X-Ray Diffraction