Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome

Tsung Wei Su, Chao Yu Yang, Wen Pin Kao, Bai Jiun Kuo, Shan Meng Lin, Jung Yaw Lin, Yu Chih Lo, Su Chang Lin

研究成果: Article同行評審

7 引文 斯高帕斯(Scopus)

摘要

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly.

原文English
頁(從 - 到)407-420
頁數14
期刊Structure
25
發行號3
DOIs
出版狀態Published - 2017 三月 7

All Science Journal Classification (ASJC) codes

  • 結構生物學
  • 分子生物學

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