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. 2022 Sep 6;25(10):105064. doi: 10.1016/j.isci.2022.105064

Figure 4.

Figure 4

SJ572946 and A3 cooperate with BID BH3 in BAK-mediated liposome permeabilization

(A) Model of direct BAK activation by BID BH3, compounds SJ572946 and A3, and their combination.

(B) Results of liposome permeabilization assays, quantified as the AUCs of the kinetic traces from Figure S5A, revealing the cooperation of WT BID BH3 and SJ572946 or A3 in direct BAK activation. Data are presented as the mean +SE of n = 2 experiments, each comprising n = 3 technical replicates, ∗∗p <0.0021, ∗p <0.0332; Tukey–Kramer one-way ANOVA.

(C) Docking of SJ572946 at pocket (3) of the activation groove of BAK, modeled based on the peptide-excluded, opened inactivated complex W3W5 BID BH3–BAK.

(D) Results of liposome permeabilization assays, quantified as the AUCs of kinetic traces from Figure S5B, revealing the cooperation of W3W5 BID BH3 and SJ572946 in direct BAK activation. W3W5 BID BH3 is inactivating and high doses and activating at low doses, as previously described (Singh et al., 2022). Data are presented as the mean +SE of n = 2 experiments, each comprising n = 3 technical replicates. ∗∗p <0.0021; Tukey–Kramer one-way ANOVA.