Perforin -- a critical protein

　

Cell-destroying 'death protein'

to fight disease

by Amy Coopes, Agence France-Presse, November 1, 2011 　
SYDNEY: Australian and British researchers uncovered the structure of a 'death protein' that destroys rogue cells – a two-billion-year-old structure stolen from bacteria – which could be used to fight disease.

The protein, perforin, targets wayward cells and punches a hole in their membranes to let in killer
enzymes, said James Whisstock from Monash University in Melbourne, Australia, adding the discovery "answers a really fundamental mystery of immunity".
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"Perforin is our body's weapon of cleansing and death," said Whisstock. "It breaks into cells that have been hijacked by viruses or turned into cancer cells and allows toxic enzymes in, to destroy the cell from within," he said. "Without it, our immune system can't destroy these cells."

A structure stolen from bacteria
Using the Australian Synchrotron in Melbourne and powerful electron microscopes at London's Birkbeck College allowed scientists to examine perforin's structure and function, Whisstock said, revealing a "powerful molecule" that targets malignant or infected cells.

Fellow researcher Joe Trapani said the 10-year study, published in Nature found that perforin's structure was similar to bacterial toxins like anthrax and listeria, suggesting that the human body had learned its tactics from diseases themselves.

"Quite remarkably that mechanism is conserved all the way back to bacteria ... we've actually pinched it off bacteria at some point [in human evolution] and turned it back against them," said Trapani, from Melbourne's Peter MacCallum Cancer Centre.

"Two billion year old blueprint"
It's a war conducted between our immune system and bacteria and we're actually fighting using similar weapons," he said, explaining that it was two billion year old blueprint.

Without perforin – released by 'killer' cells designed to destroy harmful invaders – the body was unable to fight infections. Studies with mice had linked defective perforin to leukaemia and heightened cell malignancy.

The discovery also had implications for autoimmune diseases such as juvenile type 1 diabetes and for transplant patients, with the protein linked to both the elimination of healthy cells and tissue rejection, added Whisstock.

http://www.cosmosmagazine.com/news/3839/cell-destroying-death-protein-fight-disease