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Publication Abstract from PubMed

Autocatalytic activation of an initiator caspase triggers the onset of apoptosis. In dying cells, caspase-9 activation is mediated by a multimeric adaptor complex known as the Apaf-1 apoptosome. The molecular mechanism by which caspase-9 is activated by the Apaf-1 apoptosome remains largely unknown. Here we demonstrate that the previously reported 1:1 interaction between Apaf-1 caspase recruitment domain (CARD) and caspase-9 CARD is insufficient for the activation of caspase-9. Rather, formation of a multimeric CARD:CARD assembly between Apaf-1 and caspase-9, which requires three types of distinct interfaces, underlies caspase-9 activation. Importantly, an additional surface area on the multimeric CARD assembly is essential for caspase-9 activation. Together, these findings reveal mechanistic insights into the activation of caspase-9 by the Apaf-1 apoptosome and support the induced conformation model for initiator caspase activation by adaptor complexes.

Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.,Hu Q, Wu D, Chen W, Yan Z, Yan C, He T, Liang Q, Shi Y Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16254-61. doi:, 10.1073/pnas.1418000111. Epub 2014 Oct 13. PMID:25313070^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.