Title | Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Qi, 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 |
Journal | Cell |
Volume | 141 |
Issue | 3 |
Pagination | 446-57 |
Date Published | 2010 Apr 30 |
ISSN | 1097-4172 |
Keywords | Amino 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 | <p>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.</p> |
DOI | 10.1016/j.cell.2010.03.017 |
Alternate Journal | Cell |
PubMed ID | 20434985 |
Grant List | R01 AI070285 / AI / NIAID NIH HHS / United States R01 GM074985 / GM / NIGMS NIH HHS / United States S10 RR025415 / RR / NCRR NIH HHS / United States |