Download MendeleyDark and Dronc activation in Drosophila melanogaster.
Tian, L., Li, Y., Shi, Y.(2024) Proc Natl Acad Sci U S A 121: e2312784121-e2312784121
- PubMed: 38381783
- DOI: https://doi.org/10.1073/pnas.2312784121
- Primary Citation of Related Structures:
8Y6P - PubMed Abstract:
The onset of apoptosis is characterized by a cascade of caspase activation, where initiator caspases are activated by a multimeric adaptor complex known as the apoptosome. In Drosophila melanogaster , the initiator caspase Dronc undergoes autocatalytic activation in the presence of the Dark apoptosome. Despite rigorous investigations, the activation mechanism for Dronc remains elusive. Here, we report the cryo-EM structures of an auto-inhibited Dark monomer and a single-layered, multimeric Dark/Dronc complex. Our biochemical analysis suggests that the auto-inhibited Dark oligomerizes upon binding to Dronc, which is sufficient for the activation of both Dark and Dronc. In contrast, the previously observed double-ring Dark apoptosome may represent a non-functional or "off-pathway" conformation. These findings expand our understanding on the molecular mechanism of apoptosis in Drosophila .
Organizational Affiliation:
Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
