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Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.

Abstract：

: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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Hu Q,Wu D,Chen W,Yan Z,Yan C,He T,Liang Q,Shi Y

doi

10.1073/pnas.1418000111

subject

Has Abstract

pub_date

2014-11-18 00:00:00

pages

16254-61

issue

46

eissn

0027-8424

issn

1091-6490

pii

1418000111

journal_volume

111

pub_type

杂志文章

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