College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Department of Biotechnology, Konkuk University, Chungju, Chungbuk 27478, Republic of Korea.
Acta Crystallogr D Struct Biol. 2021 Dec 1;77(Pt 12):1543-1553. doi: 10.1107/S2059798321010767. Epub 2021 Nov 11.
The cell-death-inducing DFF45-like effector (CIDE) domain is a protein-interaction module comprising ∼80 amino acids and was initially identified in several apoptotic nucleases and their regulators. CIDE-domain-containing proteins were subsequently identified among proteins involved in lipid metabolism. Given the involvement of CIDE-domain-containing proteins in cell death and lipid homeostasis, their structure and function have been intensively studied. Here, the head-to-tail helical filament structure of the CIDE domain of DNA fragmentation factor-related protein 3 (DREP3) is presented. The helical filament structure was formed by opposing positively and negatively charged interfaces of the domain and was assembled depending on protein and salt concentrations. Although conserved filament structures are observed in CIDE family members, the structure elucidated in this study and its comparison with previous structures indicated that the size and the number of molecules used in one turn vary. These findings suggest that this charged-surface-based head-to-tail helical filament structure represents a unified mechanism of CIDE-domain assembly and provides insight into the function of various forms of the filament structure of the CIDE domain in higher-order assembly for apoptotic DNA fragmentation and control of lipid-droplet size.
细胞死亡诱导的 DFF45 样效应物（CIDE）结构域是一种由约 80 个氨基酸组成的蛋白相互作用模块，最初在几种凋亡核酶及其调节剂中被鉴定出来。随后，在参与脂质代谢的蛋白中发现了含有 CIDE 结构域的蛋白。鉴于 CIDE 结构域蛋白在细胞死亡和脂质动态平衡中的参与，它们的结构和功能已得到深入研究。本文展示了 DNA 片段化因子相关蛋白 3（DREP3）的 CIDE 结构域的从头至尾螺旋丝结构。该螺旋丝结构由该结构域的正电荷和负电荷界面形成，并且根据蛋白质和盐浓度组装。尽管在 CIDE 家族成员中观察到保守的丝状结构，但在这项研究中阐明的结构及其与先前结构的比较表明，一个螺旋中使用的分子大小和数量不同。这些发现表明，这种基于带电表面的头对头螺旋丝结构代表了 CIDE 结构域组装的统一机制，并为 CIDE 结构域的各种形式的丝状结构在凋亡性 DNA 片段化的高级组装和对脂滴大小的控制中的功能提供了深入了解。
