Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation
- PMID: 11864614
- DOI: 10.1016/s1097-2765(02)00442-2
Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation
Abstract
The apoptosome is an Apaf-1 cytochrome c complex that activates procaspase-9. The three-dimensional structure of the apoptosome has been determined at 27 A resolution, to reveal a wheel-like particle with 7-fold symmetry. Molecular modeling was used to identify the caspase recruitment and WD40 domains within the apoptosome and to infer likely positions of the CED4 homology motif and cytochrome c. This analysis suggests a plausible role for cytochrome c in apoptosome assembly. In a subsequent structure, a noncleavable mutant of procaspase-9 was localized to the central region of the apoptosome. This complex promotes the efficient activation of procaspase-3. Therefore, the cleavage of procaspase-9 is not required to form an active cell death complex.
Similar articles
-
Apoptosome: the cellular engine for the activation of caspase-9.Structure. 2002 Mar;10(3):285-8. doi: 10.1016/s0969-2126(02)00732-3. Structure. 2002. PMID: 12005427 Review.
-
Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.Nat Cell Biol. 2000 Aug;2(8):469-75. doi: 10.1038/35019501. Nat Cell Biol. 2000. PMID: 10934466
-
Negative regulation of cytochrome c-mediated oligomerization of Apaf-1 and activation of procaspase-9 by heat shock protein 90.EMBO J. 2000 Aug 15;19(16):4310-22. doi: 10.1093/emboj/19.16.4310. EMBO J. 2000. PMID: 10944114 Free PMC article.
-
Regulation of the Apaf-1/caspase-9 apoptosome by caspase-3 and XIAP.J Biol Chem. 2003 Mar 7;278(10):8091-8. doi: 10.1074/jbc.M204783200. Epub 2002 Dec 27. J Biol Chem. 2003. PMID: 12506111
-
Portrait of a killer: the mitochondrial apoptosome emerges from the shadows.Mol Interv. 2003 Feb;3(1):19-26. doi: 10.1124/mi.3.1.19. Mol Interv. 2003. PMID: 14993435 Review.
Cited by
-
The role of regulated necrosis in endocrine diseases.Nat Rev Endocrinol. 2021 Aug;17(8):497-510. doi: 10.1038/s41574-021-00499-w. Epub 2021 Jun 16. Nat Rev Endocrinol. 2021. PMID: 34135504 Free PMC article. Review.
-
Activation and regulation of the inflammasomes.Nat Rev Immunol. 2013 Jun;13(6):397-411. doi: 10.1038/nri3452. Nat Rev Immunol. 2013. PMID: 23702978 Free PMC article. Review.
-
Cell differentiation: reciprocal regulation of Apaf-1 and the inhibitor of apoptosis proteins.J Cell Biol. 2004 Oct 25;167(2):193-5. doi: 10.1083/jcb.200409171. J Cell Biol. 2004. PMID: 15504905 Free PMC article. Review.
-
Engineering a dimeric caspase-9: a re-evaluation of the induced proximity model for caspase activation.PLoS Biol. 2005 Jun;3(6):e183. doi: 10.1371/journal.pbio.0030183. Epub 2005 May 10. PLoS Biol. 2005. PMID: 15941357 Free PMC article.
-
TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system.Semin Immunopathol. 2007 Sep;29(3):275-88. doi: 10.1007/s00281-007-0078-z. Epub 2007 Aug 10. Semin Immunopathol. 2007. PMID: 17690885 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials