Structural domains of Bcl-2 family members.

Transmembrane (TM) domains mediate insertion into the mitochondrial outer membrane. The Bcl-2-homology (BH) domains 1, 2, and 3 of antiapoptotic family members form a hydrophobic binding pocket for BH3-only proteins. Mcl-1 encodes a unique amino terminal domain of 180 amino acids, which may be involved in functions that are unique to Mcl-1. The multidomain killers Bax and Bak can oligomerize to form pores in the outer mitochondrial membrane in a process regulated by BH3-only family members.