8JNS

cryo-EM structure of a CED-4 hexamer

Summary for 8JNS

• Entry DOI: 10.2210/pdb8jns/pdb
• EMDB information: 36450
• Descriptor: Cell death protein 4, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: ced-4 apoptosome, hexamer, apoptosis
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 9
• Total formula weight: 569768.31

Authors

Li, Y.,Shi, Y. (deposition date: 2023-06-06, release date: 2023-06-28, Last modification date: 2024-07-03)

Primary citation

Li, Y.,Tian, L.,Zhang, Y.,Shi, Y.
Structural insights into CED-3 activation.
Life Sci Alliance, 6:-, 2023

PubMed Abstract: In , onset of programmed cell death is marked with the activation of CED-3, a process that requires assembly of the CED-4 apoptosome. Activated CED-3 forms a holoenzyme with the CED-4 apoptosome to cleave a wide range of substrates, leading to irreversible cell death. Despite decades of investigations, the underlying mechanism of CED-4-facilitated CED-3 activation remains elusive. Here, we report cryo-EM structures of the CED-4 apoptosome and three distinct CED-4/CED-3 complexes that mimic different activation stages for CED-3. In addition to the previously reported octamer in crystal structures, CED-4, alone or in complex with CED-3, exists in multiple oligomeric states. Supported by biochemical analyses, we show that the conserved CARD-CARD interaction promotes CED-3 activation, and initiation of programmed cell death is regulated by the dynamic organization of the CED-4 apoptosome.

PubMed: 37402593
DOI: 10.26508/lsa.202302056

Experimental method

ELECTRON MICROSCOPY (4.2 Å)