Structural insights into CED-3 activation.

Autor:	Li Y; Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China liyini@mail.tsinghua.edu.cn., Tian L; Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China., Zhang Y; Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China., Shi Y; Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China shi-lab@tsinghua.edu.cn.; Westlake Laboratory of Life Science and Biomedicine, Westlake Institute for Advanced Study, Hangzhou, China.; Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, China.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2023 Jul 04; Vol. 6 (9). Date of Electronic Publication: 2023 Jul 04 (Print Publication: 2023).
DOI:	10.26508/lsa.202302056
Abstrakt:	In Caenorhabditis elegans (C. elegans) , 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. (© 2023 Li et al.)
Databáze:	MEDLINE
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