BAX is the cytosolic counterpart to BAK among the apoptotic effectors. It is held largely in the cytosol in healthy cells and translocates to the mitochondrial outer membrane on activation, where it oligomerises and permeabilises the membrane. This peptide corresponds to the BAX BH3 domain, the amphipathic helix that mediates its interactions within the family. What distinguishes work on the BAX BH3 peptide is how much of its activity depends on physical form rather than sequence alone. A study of sequence and helicity requirements for the proapoptotic activity of BAX BH3 peptides found that the peptide must be able to adopt its helical conformation to function, which is why stapled and otherwise conformationally constrained versions of this domain became a major line of drug discovery. Separate work in membranes showed that the BAX BH3 H2-H3 peptide promotes apoptosis by inhibiting both the pore-forming and the anti-BAX activities of BCL-2, meaning its behaviour in a lipid environment is not simply predicted by solution binding data. For experimental design, that has a practical consequence: results with this peptide can depend on whether the assay is run in solution, on liposomes, or in permeabilised cells, and a negative result in one format does not rule out activity in another. The matched L to A substituted version (LT1046) is the appropriate paired control for attributing an observed effect to BH3 binding. | 