Formation of Apoptosome Is Initiated by Cytochrome c-Induced dATP Hydrolysis and Subsequent Nucleotide Exchange on Apaf-1
Apoptosis in metazoans is executed by a group of intracellular proteases named caspases. One of the caspase-activating pathways in mammals is initiated by the release of cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-activating heptameric protein complex n...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 49; pp. 17545 - 17550 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
06.12.2005
National Acad Sciences |
Series | Inaugural Article |
Subjects | |
Online Access | Get full text |
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Summary: | Apoptosis in metazoans is executed by a group of intracellular proteases named caspases. One of the caspase-activating pathways in mammals is initiated by the release of cytochrome c from mitochondria to cytosol, where it binds to Apaf-1 to form a procaspase-9-activating heptameric protein complex named apoptosome. We report here the reconstitution of this pathway with purified recombinant Apaf-1, procaspase-9, procaspase-3, and cytochrome c from horse heart. Apaf-1 contains a dATP as a cofactor. Cytochrome c binding to Apaf-1 induces hydrolysis of dATP to dADP, which is subsequently replaced by exogenous dATP. The dATP hydrolysis and exchange on Apaf-1 are two required steps for apoptosome formation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 To whom correspondence should be addressed. E-mail: xwang@biochem.swmed.edu. This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on April 20, 2004. Conflict of interest statement: No conflicts declared. Contributed by Xiaodong Wang, September 13, 2005 Author contributions: H.-E.K., F.D., M.F., and X.W. designed research; H.-E.K., F.D., and M.F. performed research; F.D. contributed new reagents/analytic tools; H.-E.K., M.F., and X.W. analyzed data; and H.-E.K. and X.W. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0507900102 |