Unlatched BAX pairs for death

Abstract

Self-interacting BAX proteins permeabilize outer mitochondrial membranes to trigger apoptotic cell death. Czabotar et al. present two revealing structures of BAX dimers: one dimer has an activator BH3 helix bound into its canonical cleft, and the other dimer exposes a planar hydrophobic face potentially critical for membrane interactions.

Figure 1

Novel BAX dimer structure reveals potential membrane interaction face. (A) Schematic of two dimer structures presented in Czabotar et al. (B) Novel “core” dimer structure of BAX formed by swapping the BH3 (helix 2) of one molecule into the position of the BH3 (helix 2) of the other molecule to create a relatively flat hydrophobic surface consisting of helices 4 and 5. Diagram represents a top-down view of the dimer with a membrane in the plane of the page. The locations of helices α1 and α6-α8 are inferred, and are in gray-color to delineate. (C) Rotated view of the central α4-α5 helices, in which twelve bulky hydrophobic side chains orient towards the membrane. Helices may either directly embed into the membrane to alter membrane structure, or possibly reorient to form the α5-α6 helical hairpin. Lipids in bold indicate displacement of molecules due to helix integration into the membrane, leading to changes in membrane curvature.