The carboxyl-terminal sequence of bim enables bax activation and killing of unprimed cells
| العنوان: | The carboxyl-terminal sequence of bim enables bax activation and killing of unprimed cells |
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| المؤلفون: | Zhi Zhang, Dang Nguyen, Xiaoke Chi, David W. Andrews, Elizabeth J Osterlund, Hetal Brahmbhatt, Brian Leber, James M. Pemberton, Jialing Lin, Qian Liu |
| المصدر: | eLife eLife, Vol 9 (2020) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Structural Biology and Molecular Biophysics, Mutant, Sequence (biology), Mitochondrion, 0302 clinical medicine, hemic and lymphatic diseases, Biology (General), Inner mitochondrial membrane, Cells, Cultured, bcl-2-Associated X Protein, mitochondrial outer membrane permeabilization, Cerebral Cortex, Neurons, 0303 health sciences, Bcl-2-Like Protein 11, Chemistry, General Neuroscience, apoptosis, General Medicine, BMK cells, Cell biology, Mitochondria, Membrane, 030220 oncology & carcinogenesis, Mitochondrial Membranes, Molecular mechanism, Medicine, biological phenomena, cell phenomena, and immunity, Research Article, QH301-705.5, Science, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Protein Domains, None, Animals, Humans, MEF cells, 030304 developmental biology, General Immunology and Microbiology, Molecular biophysics, Cell Biology, HCT116 Cells, nervous system diseases, Bcl-2 family proteins, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, Structural biology, Apoptosis, primary murine neurons |
| الوصف: | The Bcl-2 family BH3 protein Bim promotes apoptosis at mitochondria by activating the pore forming proteins Bax and Bak and by inhibiting the anti-apoptotic proteins Bcl-XL, Bcl-2 and Mcl-1. Bim binds to these proteins via its BH3 domain and to the mitochondrial membrane by a carboxyl-terminal sequence (CTS). In cells killed by Bim, the expression of a Bim mutant in which the CTS was deleted (BimL-dCTS) triggered variable amounts of apoptosis that correlated with inhibition of anti-apoptotic proteins being sufficient to permeabilize mitochondria isolated from the same cells. Detailed analysis of the molecular mechanism demonstrated that BimL-dCTS inhibited Bcl-XL but did not activate Bax. Our examination of additional point mutants unexpectedly revealed that the CTS of Bim is required for physiological concentrations of Bim to activate Bax and that different residues in the CTS enable Bax activation and binding to membranes. |
| تدمد: | 2050-084X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2fea2501e20063cec39d32828271031dTest https://pubmed.ncbi.nlm.nih.gov/31976859Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2fea2501e20063cec39d32828271031d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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