CED-4 Apoptosome
<StructureSection load="3lqq" size="350" color="" frame="true" spin="on" Scene='3lqq/Default/1' side="right" caption="Nematode CED-4 apoptosome complex with ATP and Mg+2 ion 3lqq" >
Structure of the CED-4 Apoptosome (3lqq)
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.
Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4., 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, Cell. 2010 Apr 30;141(3):446-57. PMID:20434985
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3lqq is a 2 chains structure with sequences from Caenorhabditis elegans. Full crystallographic information is available from OCA.
The crystallographic asymmetric unit of the solved structure is an asymmetric dimer of CED-4. Morph showing how each monomer in the asymmetric dimer relate to each other. Be sure to spin it around because from the side it is easier to see the dramatic difference.
The biological molecule is an octamer (tetramer of the asymmetric dimer) that forms a shape similar to a funnel.
External Links
- Structural biology: The funnel of death by Felix Cheung at Nature China.
Created with the participation of Wayne Decatur, Eran Hodis.
