التفاصيل البيبلوغرافية
| العنوان: |
Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes |
| المؤلفون: |
Chao-Yu Yang, Yi-Chun Tseng, Yi-Fan Tu, Bai-Jiun Kuo, Li-Chung Hsu, Chia-I Lien, You-Sheng Lin, Yin-Ting Wang, Yen-Chen Lu, Tsung-Wei Su, Yu-Chih Lo, Su-Chang Lin |
| المصدر: |
Nature Communications, Vol 15, Iss 1, Pp 1-17 (2024) |
| بيانات النشر: |
Nature Portfolio, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Science |
| مصطلحات موضوعية: |
Science |
| الوصف: |
Abstract cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-53306-1 |
| URL الوصول: |
https://doaj.org/article/b5842367d1a0401d8ba54c4ee9b33b37 |
| رقم الانضمام: |
edsdoj.b5842367d1a0401d8ba54c4ee9b33b37 |
| قاعدة البيانات: |
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