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

TitleCrystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4.
Publication TypeJournal Article
Year of Publication2010
AuthorsQi, S, Pang, Y, Hu, Q, Liu, Q, Li, H, Zhou, Y, He, T, Liang, Q, Liu, Y, Yuan, X, Luo, G, Li, H, Wang, J, Yan, N, Shi, Y
JournalCell
Volume141
Issue3
Pagination446-57
Date Published2010 Apr 30
ISSN1097-4172
KeywordsAmino Acid Sequence, Animals, Apoptosomes, Apoptotic Protease-Activating Factor 1, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Calcium-Binding Proteins, Caspases, Crystallography, X-Ray, Models, Molecular, Sequence Alignment, X-Ray Diffraction
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.

DOI10.1016/j.cell.2010.03.017
Alternate JournalCell
PubMed ID20434985
Grant ListR01 AI070285 / AI / NIAID NIH HHS / United States
R01 GM074985 / GM / NIGMS NIH HHS / United States
S10 RR025415 / RR / NCRR NIH HHS / United States