Apoptotic DNA fragmentation and chromatin condensation are mediated by the caspase-activated DFF40/CAD nuclease, which is chaperoned and inhibited by DFF45/ICAD. CIDE proteins share a homologous regulatory CIDE-N domain with DFF40/CAD and DFF45/ICAD. Here we report the solution structure of CIDE-N of human CIDE-B. We show that the CIDE-N of CIDE-B interacts with CIDE-N domains of both DFF40 and DFF45. The binding epitopes are similar and map to a highly charged bipolar surface region of CIDE-B. Furthermore, we demonstrate that the CIDE-N of CIDE-B regulates enzymatic activity of the DFF40/DFF45 complex in vitro. Based on these results and mutagenesis data, we propose a model for the CIDE-N/CIDE-N complex and discuss the role of this novel bipolar interaction in mediating downstream events of apoptosis.
