Bax is a pro-apoptotic member of the Bcl-2 family of proteins. It contains the three Bcl-2 homology domains BH1, BH2 and BH3 that are involved in protein–protein interaction. In healthy cells Bax is ‘dormant’, located in the cytosol or loosely associated to mitochondria. Upon induction of apoptosis, the protein was shown to translocate to mitochondria, insert into the outer membrane, oligomerize and trigger the release of cytochrome c, Smac/Diablo and other proteins from the intermembrane space. These events require various conformational changes of the protein: why? The recent resolution of the 3D structure of full length monomeric Bax by Suzuki et al1 has brought a new insight into the requirement for structural modifications, and the mechanism through which these may occur.

The structure of Bax consists of eight amphipathic helices clustered around helix α5, that constitute the hydrophobic core of the protein. The overall folding of Bax is similar to that of Bcl-xL2 and Bid,3,4 two other members of the Bcl-2 family whose structure had previously been resolved. Like these two proteins, Bax displays a structure reminiscent of the structure of the transmembrane domain of the bacterial toxins, diphteria toxin and colicins, which act as channels for ions and peptides. Whether Bax, Bcl-xL and Bid form such channels into the mitochondrial membrane is an interesting possibility but this has not yet been demonstrated.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD