AI Article Synopsis
- BAX is a protein responsible for inducing apoptosis by changing from a single unit (monomer) to a more complex, toxic structure (oligomer) that disrupts the outer membrane of mitochondria, but how this process works is not fully understood.
- The study focused on creating a pure form of BAX that mimics its natural activation, which allowed researchers to investigate how the protein's structure changes during oligomerization and its role in membrane permeabilization.
- Findings identified key regions within the BAX protein, particularly specific residues and alpha helices, that are vital for different steps in the activation process, offering new insights into how BAX contributes to cell death during mitochondrial apoptosis.
Article Abstract
BAX is a pro-apoptotic protein that transforms from a cytosolic monomer into a toxic oligomer that permeabilizes the mitochondrial outer membrane. How BAX monomers assemble into a higher-order conformation, and the structural determinants essential to membrane permeabilization, remain a mechanistic mystery. A key hurdle has been the inability to generate a homogeneous BAX oligomer (BAX) for analysis. Here, we report the production and characterization of a full-length BAX that recapitulates physiologic BAX activation. Multidisciplinary studies revealed striking conformational consequences of oligomerization and insight into the macromolecular structure of oligomeric BAX. Importantly, BAX enabled the assignment of specific roles to particular residues and α helices that mediate individual steps of the BAX activation pathway, including unexpected functionalities of BAX α6 and α9 in driving membrane disruption. Our results provide the first glimpse of a full-length and functional BAX, revealing structural requirements for the elusive execution phase of mitochondrial apoptosis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472837 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2020.05.029 | DOI Listing |
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