title: Fifty C-terminal amino acid residues are necessary for the chaperone activity of DFF45 but not for the inhibition of DFF40.
abstract: Apoptotic DNA fragmentation, the hallmark of apoptosis, is mediated primarily by caspase-activated DFF40 (CAD) nuclease. DFF40 exists as a heterodimer with DFF45 (ICAD), which is a specific chaperone and inhibitor of DFF40 under normal conditions. To understand the mechanism through which the DFF40/DFF45 system is regulated, we analyzed the structural and biochemical properties of apoptotic DNA fragmentation mediated by DFF40/DFF45. Using limited proteolysis, we show that residues 1-281 of DFF45 form a rigid, crystallized domain, whereas the loop formed by residues 277-281 is accessible by trypsin. These results show that the C-terminal helix formed by residues 281-300 is dynamic and necessary for the chaperone activity of DFF45, but not for inhibition of DFF40.
authors: Department of Biochemistry, School of Biotechnology, Yeungnam University, Gyeongsan, South Korea. hyunho@ynu.ac.kr
authors: Hyun Ho
authors: HH
authors: Park
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D051017:Apoptosis Regulatory Proteins; D003460:Crystallization; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors*; D018832:Molecular Chaperones / Q000737:chemistry / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D000596:Amino Acids; D051017:Apoptosis Regulatory Proteins; D018832:Molecular Chaperones; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; C109664:caspase-activated DNase inhibitor; C113696:DFFB protein, human; D003851:Deoxyribonucleases