AI Article Synopsis
- The pro-apoptotic BAX protein usually resides in the cytosol of healthy cells but migrates to mitochondria when apoptosis is triggered, forming oligomers.
- Researchers successfully captured and analyzed the structure of activated BAX oligomers using spectroscopic techniques, revealing how these oligomers form from homodimers.
- Findings indicate that the soluble oligomers can directly convert into membrane-inserted forms, which induce apoptosis, and highlight structural differences that suggest a new pathway for apoptosis involving oligomer formation before membrane insertion.
Article Abstract
Proapoptotic BAX protein is largely cytosolic in healthy cells, but it oligomerizes and translocates to mitochondria upon receiving apoptotic stimuli. A long-standing challenge has been the inability to capture any structural information beyond the onset of activation. Here, we present solution structures of an activated BAX oligomer by means of spectroscopic and scattering methods, providing details about the monomer-monomer interfaces in the oligomer and how the oligomer is assembled from homodimers. We show that this soluble oligomer undergoes a direct conversion into membrane-inserted oligomer, which has the ability of inducing apoptosis and structurally resembles a membrane-embedded oligomer formed from BAX monomers in lipid environment. Structural differences between the soluble and the membrane-inserted oligomers are manifested in the C-terminal helices. Our data suggest an alternative pathway of apoptosis in which BAX oligomer formation occurs prior to membrane insertion.
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| http://dx.doi.org/10.1016/j.str.2015.07.013 | DOI Listing |
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