Structure of Bax: Coregulation of Dimer Formation and Intracellular Localization

Apoptosis is stimulated by the insertion of Bax from the cytosol into mitochondrial membranes. The solution structure of Bax, including the putative transmembrane domain at the C terminus, was determined in order to understand the regulation of its subcellular location. Bax consists of 9 α helices where the assembly of helices α1 through α8 resembles that of the apoptosis inhibitor, Bcl-xL. The C-terminal α9 helix occupies the hydrophobic pocket proposed previously to mediate heterodimer formation and bioactivity of opposing members of the Bcl-2 family. The Bax structure shows that the orientation of helix α9 provides simultaneous control over its mitochondrial targeting and dimer formation.