Apoptosis is a process that causes cell death. It can go awry in cancer cells, sustaining the disease. Scientists at St. Jude Children's Research Hospital have captured the structure of BAK, a protein that triggers apoptosis. They have shown how BAK autoactivates, essentially turning itself on. Understanding how apoptosis is triggered can lead to drugs that kill cancer cells. The findings were published online today in Nature Communications.

Apoptosis is kick-started by proteins, including BAK, that form pores on the membrane of mitochondria. BAK has to be turned on to work, but the activation process is brief and elusive. BAK can be turned on by either direct activation or autoactivation. Direct activation is a well-studied process where proteins such as BID and BIM turn on BAK. Autoactivation is a less understood process where an active BAK molecule turns on an inactive one.

"Our work shows how BAK autoactivates," said corresponding author Tudor Moldoveanu, Ph.D., St. Jude Departments of Structural Biology and Chemical Biology and Therapeutics. "Once an active BAK is produced through direct activation by BID or BIM, which are upstream activators, then that active BAK can go and turn on dormant BAK."