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-Structure paper
Title | Structural insights into CED-3 activation. |
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Journal, issue, pages | Life Sci Alliance, Vol. 6, Issue 9, Year 2023 |
Publish date | Jul 4, 2023 |
Authors | Yini Li / Lu Tian / Ying Zhang / Yigong Shi / |
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 ...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. |
External links | Life Sci Alliance / PubMed:37402593 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 - 4.2 Å |
Structure data | EMDB-36450, PDB-8jns: EMDB-36451, PDB-8jo0: EMDB-36459, PDB-8jol: |
Chemicals | ChemComp-MG: ChemComp-ATP: |
Source |
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Keywords | APOPTOSIS / CED-4 apoptosome / Hexamer / CED-4 / CED-3 catalytic domain / CED-3 / holoenzyme |