Crystal Structure of the Caenorhabditis elegans Apoptosome Reveals an Octameric Assembly of CED-4
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{sup +} 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{sup +} ATPases and suggests a mechanism for the activation of CED-3.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- LABORATORY-DIRECTED RESEARCH AND DEVELOPMENT
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1014300
- Report Number(s):
- BNL-93656-2010-JA; CELLB5; R&D Project: 06-060; YN0100000; TRN: US201111%%253
- Journal Information:
- Cell, Vol. 141, Issue 3; ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- English
Similar Records
Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans
Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans