Solution structure of the CIDE-N domain of CIDE-B and a model for CIDE-N/CIDE-N interactions in the DNA fragmentation pathway of apoptosis.
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.
Lugovskoy
A A
AA
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA.
Zhou
P
P
Chou
J J
JJ
McCarty
J S
JS
Li
P
P
Wagner
G
G
D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D053938:DNA Fragmentation; D003851:Deoxyribonucleases / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment
D051017:Apoptosis Regulatory Proteins; C112511:CIDEB protein, human; D011506:Proteins; C109664:caspase-activated DNase inhibitor; D003851:Deoxyribonucleases