School of Chemistry and Biochemistry and Graduate School of Biochemistry, Yeungnam University, Gyeongsan 712-749, South Korea.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):7361-7366. doi: 10.1073/pnas.1705949114. Epub 2017 Jun 26.
Cell death-inducing DFF45-like effector (CIDE) domains, initially identified in apoptotic nucleases, form a family with diverse functions ranging from cell death to lipid homeostasis. Here we show that the CIDE domains of and human apoptotic nucleases Drep2, Drep4, and DFF40 all form head-to-tail helical filaments. Opposing positively and negatively charged interfaces mediate the helical structures, and mutations on these surfaces abolish nuclease activation for apoptotic DNA fragmentation. Conserved filamentous structures are observed in CIDE family members involved in lipid homeostasis, and mutations on the charged interfaces compromise lipid droplet fusion, suggesting that CIDE domains represent a scaffold for higher-order assembly in DNA fragmentation and other biological processes such as lipid homeostasis.
细胞死亡诱导型 DFF45 样效应物（CIDE）结构域最初在凋亡核酶中被发现，形成了一个具有多种功能的家族，从细胞死亡到脂质稳态。在这里，我们表明， 和人类凋亡核酶 Drep2、Drep4 和 DFF40 的 CIDE 结构域都形成了头尾相连的螺旋丝。相反的正电荷和负电荷界面介导了螺旋结构，这些表面的突变会使凋亡 DNA 片段化的核酶激活。在参与脂质稳态的 CIDE 家族成员中观察到保守的丝状结构，而在带电界面上的突变会破坏脂质滴融合，这表明 CIDE 结构域代表了 DNA 片段化和其他生物学过程（如脂质稳态）中高级组装的支架。
