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| Title | Dark and Dronc activation in . |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 121, Issue 9, Page e2312784121, Year 2024 |
| Publish date | Feb 27, 2024 |
 Authors | Lu Tian / Yini Li / Yigong Shi /  |
| 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 , the initiator caspase ...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 , 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 . |
 External links | Proc Natl Acad Sci U S A / PubMed:38381783 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.9 - 7.0 Å |
| Structure data | EMDB-38994, PDB-8y6p: EMDB-38995, PDB-8y6q: |
| Source |
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 Keywords | APOPTOSIS / Dark / cryo-EM / Dronc |
drosophila melanogaster (fruit fly)