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https://hdl.handle.net/2440/117724
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Type: | Journal article |
Title: | New insights into apoptosome structure and function |
Author: | Dorstyn, L. Akey, C.W. Kumar, S. |
Citation: | Cell Death and Differentiation, 2018; 25(7):1194-1208 |
Publisher: | Springer Nature |
Issue Date: | 2018 |
ISSN: | 1350-9047 1476-5403 |
Statement of Responsibility: | Loretta Dorstyn, Christopher W. Akey, Sharad Kumar |
Abstract: | The apoptosome is a platform that activates apical procaspases in response to intrinsic cell death signals. Biochemical and structural studies in the past two decades have extended our understanding of apoptosome composition and structure, while illuminating the requirements for initiator procaspase activation. A number of studies have now provided high-resolution structures for apoptosomes from C. elegans (CED-4), D. melanogaster (Dark), and H. sapiens (Apaf-1), which define critical protein interfaces, including intra and interdomain interactions. This work also reveals interactions of apoptosomes with their respective initiator caspases, CED-3, Dronc and procaspase-9. Structures of the human apoptosome have defined the requirements for cytochrome c binding, which triggers the conversion of inactive Apaf-1 molecules to an extended, assembly competent state. While recent data have provided a detailed understanding of apoptosome formation and procaspase activation, they also highlight important evolutionary differences with functional implications for caspase activation. |
Keywords: | Animals Humans Drosophila melanogaster Caenorhabditis elegans Caenorhabditis elegans Proteins Drosophila Proteins Caspase 9 Apoptotic Protease-Activating Factor 1 Apoptosomes |
Rights: | © ADMC Associazione Differenziamento e Morte Cellulare 2018 |
DOI: | 10.1038/s41418-017-0025-z |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1021456 http://purl.org/au-research/grants/nhmrc/1043057 http://purl.org/au-research/grants/nhmrc/1103006 |
Published version: | http://dx.doi.org/10.1038/s41418-017-0025-z |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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