title: 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.
abstract: 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.
authors.affiliation: Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Lugovskoy
authors.forename: P
authors.initials: P
authors.lastname: Zhou
authors.forename: J J
authors.initials: JJ
authors.lastname: Chou
authors.forename: J S
authors.initials: JS
authors.lastname: McCarty
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Wagner
mesh_terms: 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
chemical_list: D051017:Apoptosis Regulatory Proteins; C112511:CIDEB protein, human; D011506:Proteins; C109664:caspase-activated DNase inhibitor; D003851:Deoxyribonucleases