1v0d: Difference between revisions
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==Overview== | ==Overview== | ||
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 | 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. | ||
==About this Structure== | ==About this Structure== | ||
1V0D is a | 1V0D is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN, MG and PB as [http://en.wikipedia.org/wiki/ligands ligands]. The following page contains interesting information on the relation of 1V0D with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb56_1.html Caspases]]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1V0D OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: nuclease]] | [[Category: nuclease]] | ||
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Revision as of 12:41, 5 November 2007
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CRYSTAL STRUCTURE OF CASPASE-ACTIVATED DNASE (CAD)
Overview
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.
About this Structure
1V0D is a Single protein structure of sequence from Mus musculus with ZN, MG and PB as ligands. The following page contains interesting information on the relation of 1V0D with [Caspases]. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway., Woo EJ, Kim YG, Kim MS, Han WD, Shin S, Robinson H, Park SY, Oh BH, Mol Cell. 2004 May 21;14(4):531-9. PMID:15149602
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