8y6q
From Proteopedia
Structure of the Dark/Dronc complex
Structural highlights
FunctionPublication Abstract from PubMedThe 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. Dark and Dronc activation in Drosophila melanogaster.,Tian L, Li Y, Shi Y Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2312784121. doi: , 10.1073/pnas.2312784121. Epub 2024 Feb 21. PMID:38381783[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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