4RHW

Crystal structure of Apaf-1 CARD and caspase-9 CARD complex

4RHW の概要

• エントリーDOI: 10.2210/pdb4rhw/pdb
• 分子名称: Apoptotic protease-activating factor 1, Caspase-9, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: death domain superfamily, apoptosis
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 70625.29

構造登録者

Hu, Q.,Wu, D.,Yan, C.,Shi, Y. (登録日: 2014-10-03, 公開日: 2014-10-15, 最終更新日: 2023-11-08)

主引用文献

Hu, Q.,Wu, D.,Chen, W.,Yan, Z.,Yan, C.,He, T.,Liang, Q.,Shi, Y.
Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome.
Proc. Natl. Acad. Sci. U.S.A., 111:16254-16261, 2014

PubMed 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.

PubMed: 25313070
DOI: 10.1073/pnas.1418000111

実験手法

X-RAY DIFFRACTION (2.1 Å)