DED Interaction of FADD and Caspase-8 in the Induction of Apoptotic Cell Death
| Autor: | Young-Hoon, Park, Chang Woo, Han, Mi Suk, Jeong, Se Bok, Jang |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Microbiology and Biotechnology. 32:1034-1040 |
| ISSN: | 1738-8872 1017-7825 |
| DOI: | 10.4014/jmb.2206.06003 |
| Popis: | Fas-associated death domain (FADD) is an adapter molecule that bridges the interaction between receptor-interacting protein 1 (RIP1) and aspartate-specific cysteine protease-8 (caspase-8). As the primary mediator of apoptotic cell death, caspase-8 has two N-terminal death-effector domains (DEDs) and it interacts with other proteins in the DED subfamily through several conserved residues. In the tumor necrosis receptor-1 (TNFR-1)-dependent signaling pathway, apoptosis is triggered by the caspase-8/FADD complex by stimulating receptor internalization. However, the molecular mechanism of complex formation by the DED proteins remains poorly understood. Here, we found that direct DED-DED interaction between FADD and caspase-8 and the structure-based mutations (Y8D/I128A, E12A/I128A, E12R/I128A, K39A/I128A, K39D/I128A, F122A/I128A, and L123A/I128A) of caspase-8 disrupted formation of the stable DED complex with FADD. Moreover, the monomeric crystal structure of the caspase-8 DEDs (F122A/I128A) was solved at 1.7 Å. This study will provide new insight into the interaction mechanism and structural characteristics between FADD and caspase-8 DED subfamily proteins. |
| Databáze: | OpenAIRE |
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