'Death fold' proteins can make cells self-destruct. Scientists want to control them

"One of these researchers is Randal Halfmann at the Stowers Institute for Medical Research in Kansas City, Missouri. He has been studying immune cells that self-destruct when they come into contact with molecules that present a threat to the body. "They have to somehow recognize that [threat] in this vast array of other complex molecules," he says, "and then within minutes, kill themselves." They do this much the way a soldier might dive on a grenade to save others' lives."

"Halfmann's team has been focusing on special proteins inside cells that can trigger this process. When these proteins recognize molecules associated with a virus or some other pathogen, he says, "they implode." The proteins crumple and begin linking up with other crumpled proteins to form a structure called a "death fold" polymer. That starts a chain reaction of polymerization that ultimately kills the cell."

Programmed cell death determines whether cells die prematurely or survive too long, driving Alzheimer's and cancer respectively. Excessive neuronal death contributes to neurodegeneration, while deficient tumor cell death enables cancer growth. Certain immune cells execute rapid self-destruction upon detecting threat-associated molecules via proteins that 'implode' and polymerize into 'death fold' structures, initiating a polymerization chain reaction that kills the cell. That polymerization requires a burst of energy, and investigators compared the mechanism to reusable hand warmers, which release heat when a liquid crystallizes, suggesting similar phase-change energetics could power cellular death-fold formation.

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