WEHI researchers have created the first visual structure showing how our cells undergo a form of cell death known as necroptosis.

The killer protein MLKL consists of three domains, including a killer domain which damages cell membrane to cause cell death, and a switch domain which controls the activity of MLKL. In the inactive state, the MLKL molecule is in a compact shape, with the killer domain being held in check by the brace region.

During necroptosis, a shape shift in the switch domain drives a structural change in the whole molecule, allowing 4 copies of MLKL to interact with each other, thereby releasing the killer domain into an extended conformation. The killer domains in this extended conformation can then grab onto the plasma membrane and damage it, thereby causing cell death.