Abstract
Cell death-inducing DNA fragmentation factor 45 (DFF45)-like effector (CIDE) domains were initially identified as protein interaction modules in apoptotic nucleases and are now known to form a highly conserved family with diverse functions that range from cell death to lipid homeostasis. In the fly, four CIDE domain-containing proteins (DFF-related protein [DREP]-1–4) and their functions, including interaction relationships, have been identified. In this study, we introduced and investigated acidic side-disrupted mutants of DREP1, DREP2, and DREP3. We discovered that the acidic surface patches of DREP1 and DREP3 are critical for the homo-dimerization. In addition, we found that the acidic surface sides of DREP1 and DREP3 interact with the basic surface sides of DREP2 and DREP4. Our current study provides clear evidence demonstrating the mechanism of the interactions between four DREP proteins in the fly.
Highlights
The cell death-inducing DNA fragmentation factor 45 (DFF45)-like effector (CIDE) family of proteins contains CIDE domains for protein interaction and in mammals, consists of five proteins, including DFF40, DFF45, CIDE-A, CIDE-B, and CIDE-C [1]
DFF40 and DFF45 interaction via the CIDE domain and FSP27 CIDE domain-mediated homo-dimerization are critical to apoptotic DNA fragmentation and lipid droplet formation, respectively [23,25,26]
Structural analysis of the heterodimeric structure of CIDE domains and the interaction between DFF40 and DFF45 and the homo-dimeric structure of the FSP27 CIDE domain shows that the basic surface patch of one CIDE domain interacts with the acidic surface patch of another CIDE domain [23,25,26]
Summary
The cell death-inducing DNA fragmentation factor 45 (DFF45)-like effector (CIDE) family of proteins contains CIDE domains for protein interaction and in mammals, consists of five proteins, including DFF40 (caspase-activated DNase [CAD] in mouse), DFF45 (inhibitor of CAD [ICAD] in mouse), CIDE-A, CIDE-B, and CIDE-C (fat-specific protein 27 [FSP27] in mouse) [1]. To further elucidate the mode of the CIDE domainmediated interactions of all DREP proteins in the fly system, we performed biochemical and mutational studies using acidic side-disrupted mutants of DREP1 (DREP1D62R), DREP2 (DREP2D56R), and DREP3 (DREP3D167R) (Fig 1C).
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