1V0D

Crystal Structure of Caspase-activated DNase (CAD)

Summary for 1V0D

• Entry DOI: 10.2210/pdb1v0d/pdb
• Related: 1C9F 1F2R
• Descriptor: DNA FRAGMENTATION FACTOR 40 KDA SUBUNIT, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase, nuclease, caspase-activated dnase
• Biological source: MUS MUSCULUS (MOUSE)
• Cellular location: Cytoplasm: O54788
• Total number of polymer chains: 1
• Total formula weight: 37897.58

Authors

Woo, E.-J.,Kim, Y.-G.,Kim, M.-S.,Han, W.-D.,Shin, S.,Oh, B.-H. (deposition date: 2004-03-26, release date: 2004-05-21, Last modification date: 2024-05-08)

Primary citation

Woo, E.-J.,Kim, Y.-G.,Kim, M.-S.,Han, W.-D.,Shin, S.,Robinson, H.,Park, S.-Y.,Oh, B.-H.
Structural Mechanism for Inactivation and Activation of Cad/Dff40 in the Apoptotic Pathway
Mol.Cell, 14:531-, 2004

PubMed Abstract: CAD/DFF40 is responsible for the degradation of chromosomal DNA into nucleosomal fragments and subsequent chromatin condensation during apoptosis. It exists as an inactive complex with its inhibitor ICAD/DFF45 in proliferating cells but becomes activated upon cleavage of ICAD/DFF45 into three domains by caspases in dying cells. The molecular mechanism underlying the control and activation of CAD/DFF40 was unknown. Here, the crystal structure of activated CAD/DFF40 reveals that it is a pair of molecular scissors with a deep active-site crevice that appears ideal for distinguishing internucleosomal DNA from nucleosomal DNA. Ensuing studies show that ICAD/DFF45 sequesters the nonfunctional CAD/DFF40 monomer and is also able to disassemble the functional CAD/DFF40 dimer. This capacity requires the involvement of the middle domain of ICAD/DFF45, which by itself cannot remain bound to CAD/DFF40 due to low binding affinity for the enzyme. Thus, the consequence of the caspase-cleavage of ICAD/DFF45 is a self-assembly of CAD/DFF40 into the active dimer.

PubMed: 15149602
DOI: 10.1016/S1097-2765(04)00258-8

Experimental method

X-RAY DIFFRACTION (2.6 Å)