凋亡体
黑腹果蝇
半胱氨酸蛋白酶
细胞生物学
生物
程序性细胞死亡
细胞凋亡
生物化学
基因
作者
Lü Tian,Y Li,Yigong Shi
标识
DOI:10.1073/pnas.2312784121
摘要
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 .
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