BH 3‐in‐groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes
| العنوان: | |
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| المؤلفون: | Alessandro Senes, Feng He, Xuejun C. Zhang, Justin Kale, Jingzhen Ding, Suzanne M. Lapolla, Samson G.F. Condon, Bo Huang, Zhi Zhang, Jianing Li, Sabareesh Subramaniam, David W. Andrews, Franklin A. Hays, Jialing Lin, Hetal Brahmbhatt, Chenyi Liao |
| المصدر: | The EMBO Journal. 35:208-236 |
| بيانات النشر: | EMBO, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, Dimer, Apoptosis, Mitochondrion, Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Animals, Immunoprecipitation, Molecular Biology, bcl-2-Associated X Protein, Mitochondrial outer membrane permeabilization, General Immunology and Microbiology, General Neuroscience, Articles, Cell biology, Mutational analysis, bcl-2 Homologous Antagonist-Killer Protein, 030104 developmental biology, Membrane, chemistry, Mitochondrial Membranes, Helix, Biophysics, Dimerization, Groove (joinery), Chemical labeling, Protein Binding |
| الوصف: | Pro‐apoptotic Bax induces mitochondrial outer membrane permeabilization (MOMP) by forming oligomers through a largely undefined process. Using site‐specific disulfide crosslinking, compartment‐specific chemical labeling, and mutational analysis, we found that activated integral membrane Bax proteins form a BH3‐in‐groove dimer interface on the MOM surface similar to that observed in crystals. However, after the α5 helix was released into the MOM, the remaining interface with α2, α3, and α4 helices was rearranged. Another dimer interface was formed inside the MOM by two intersected or parallel α9 helices. Combinations of these interfaces generated oligomers in the MOM. Oligomerization was initiated by BH3‐in‐groove dimerization, without which neither the other dimerizations nor MOMP occurred. In contrast, α9 dimerization occurred downstream and was required for release of large but not small proteins from mitochondria. Moreover, the release of large proteins was facilitated by α9 insertion into the MOM and localization to the pore rim. Therefore, the BH3‐in‐groove dimerization on the MOM nucleates the assembly of an oligomeric Bax pore that is enlarged by α9 dimerization at the rim. |
| تدمد: | 1460-2075 0261-4189 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::22c69ebeedff4b8990dc41c88e1d5401Test https://doi.org/10.15252/embj.201591552Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....22c69ebeedff4b8990dc41c88e1d5401 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
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