Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome
| Autor: | Bai Jiun Kuo, Yu Chih Lo, Chao Yu Yang, Wen Pin Kao, Su Chang Lin, Tsung Wei Su, Jung Yaw Lin, Shan Meng Lin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Caspase-9 biology Protomer 03 medical and health sciences Crystallography 030104 developmental biology 0302 clinical medicine Structural Biology Caspase activation biology.protein Biophysics Apoptosome Molecular Biology 030217 neurology & neurosurgery Caspase Cell survival Death domain |
| Zdroj: | Structure. 25:407-420 |
| ISSN: | 0969-2126 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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