1v0d: Difference between revisions
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==Overview== | ==Overview== | ||
CAD/DFF40 is responsible for the degradation of chromosomal DNA into | 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== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Han, W | [[Category: Han, W D.]] | ||
[[Category: Kim, M | [[Category: Kim, M S.]] | ||
[[Category: Kim, Y | [[Category: Kim, Y G.]] | ||
[[Category: Oh, B | [[Category: Oh, B H.]] | ||
[[Category: Shin, S.]] | [[Category: Shin, S.]] | ||
[[Category: Woo, E | [[Category: Woo, E J.]] | ||
[[Category: MG]] | [[Category: MG]] | ||
[[Category: PB]] | [[Category: PB]] | ||
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[[Category: nuclease]] | [[Category: nuclease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:30:15 2008'' | ||
Revision as of 13:30, 21 February 2008
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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]. Known structural/functional 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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