Do-Good Protein Related To A Brutal Toxin That Kills

Australian scientists have uncovered an unlikely family relationship between two archenemies in the disease world - a protein that fights infection and a brutal toxin that kills.

In a surprise discovery, researchers found that immune proteins enlisted by the body to fend off cancer and infection belong to an ancient and lethal toxin family previously only found in bacteria.

These bacterial toxins are responsible for deadly diseases like anthrax, flesh-eating disease, gas gangrene and scarlet fever.

The findings, published in the international journal Science, will be used to develop new ways to fight disease.

Study leader Professor James Whisstock, from the School of Biomedical Sciences at Monash University in Melbourne, said he was astounded to find these "yin and yang" fighters - proteins called perforins and nasty bacterial toxins - had a common ancestor.

"Over millions of years of evolution bacteria developed these proteins as weapons of attack," Prof Whisstock said.

"But as it turns out, animals stole that toxin from the bacteria and turned it on the enemy.

"I find that completely extraordinary. It's a molecular arms race and there's still no clear winner."

Perforins got their name because they kill bacteria, virally-infected cells and cancerous cells by punching tiny holes that perforate them.

People who lack one of these perforins can develop a serious blood disease called hemophagocytic lymphohistiocytosis, and may be predisposed to develop cancer, he said.

Prof Whisstock said certain perforins were not only important for defending humans against attack by bacteria and viruses, but also helped propagate the human species because of their role in embryo implantation.

"It is ironic that we fear diseases such as anthrax yet from the same family of toxins comes a protein that is involved in reproduction," he said.

But these proteins could also be dangerous, wreaking "absolute havoc" in the immune system if they're not controlled properly.

The researchers investigated how they work to find ways to control them in infectious diseases and areas such as transplantation rejection.

Using X-ray crystallography, the team worked out the structure of a perforin called Plu-MACPF, which, due to its similarity to the bacterial toxins, told them how the whole perforin family worked.

The findings are a culmination of nine years of research.

"Now we finally know what perforins look like and how they work, we can use this knowledge to develop new ways to fight disease," said co-author Dr Michelle Dunstone.

The research team included scientists from the National Health and Medical Research Council, the Australian Research Council and the Peter MacCallum Cancer Centre.

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