An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial␣membrane
| العنوان: | An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial␣membrane |
|---|---|
| المؤلفون: | Lingyu Du, David W. Andrews, Fujiao Lv, Yaqing Yang, Jialing Lin, Fei Qi, James J. Chou, Alessandro Piai, Justin Pogmore, Justin Kale, Maorong Wen, Bo OuYang, Shuqing Wang, Liujuan Zhou, Bin Wu, Juan del Rosario, Zhi Zhang, Zhijun Liu |
| المصدر: | The EMBO Journal |
| بيانات النشر: | EMBO, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Dimer, Lipid Bilayers, Apoptosis, Mitochondrion, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, bax core dimer, 0302 clinical medicine, Structural Biology, Amphiphile, Humans, membrane lipid bilayer, functional mutagenesis, Membrane & Intracellular Transport, Inner mitochondrial membrane, Lipid bilayer, Molecular Biology, bcl-2-Associated X Protein, 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, pore formation, General Neuroscience, Bilayer, Articles, Mitochondria, 3. Good health, Cytosol, chemistry, Mitochondrial Membranes, Biophysics, NMR structure, Autophagy & Cell Death, lipids (amino acids, peptides, and proteins), Bacterial outer membrane, 030217 neurology & neurosurgery |
| الوصف: | Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high‐resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure‐guided mutations demonstrate the importance of both types of protein–lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria. NMR structures of membrane‐bound Bax core dimer reveal dual interactions with non‐polar tails and charged heads of bilayer lipids contributing directly to apoptotic mitochondrial permeabilization. |
| تدمد: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.2020106438 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::025d03ad67615bee21c14b5d89756eeb https://doi.org/10.15252/embj.2020106438 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....025d03ad67615bee21c14b5d89756eeb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602075 02614189 |
|---|---|
| DOI: | 10.15252/embj.2020106438 |