Figure 5. Proposed charge transfer network in Bax, indicated by net changes in residue charges.

The information of the Bim-SAHB induced activation of Bax is transmitted from the Bax activation site via a charge transfer network through the core of the Bax protein, up to the Bax C- and BH3-domains. Inside the hydrophobic core of Bax, the central helix, helix 5, acts as a hub which collects and distributes charge density, mainly through residues Trp107, Arg109 and Lys119. The color coding from Figure 1 is maintained. Additionally, helix 5 is highlighted in green. The Bax residues which transfer an amount of charge of one standard deviation higher than average (Table S1) are explicitly displayed and color coded according to whether they become more positive (blue) or negative (red) upon activation. (A) The residues which transfer a significant amount of charge were found at the Bax activation site, on the loop 1–2, inside the BH groove holding the Bax C-domain, and at one end of the C-domain (see also Figure S1). Additionally, several such residues were found on helix 5, the central helix in Bax, and on the Bax BH3 domain, suggesting that the interaction at the Bax activation site is transmitted via a network of charges from the activation site, through the protein core, to the C- and BH3-domains. (B) Top view of helix 5 is given. The organization of residues Trp107, Arg109 and Lys119 inside the hydrophobic core of Bax suggests that helix 5 acts as a charge transfer hub, which integrates and distributes charge density.