Scientists from the UK and Australia have seen the human immune system's assassin a protein called perforin in action for the first time. The UK team, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust, is based at Birkbeck College where they used powerful electron microscopes to study the mechanism that perforin uses to punch holes in rogue cells. The research is published today (1800hrs, 31 October) in Nature.
Professor Helen Saibil, who leads the UK team at Birkbeck College, said "Perforin is a powerful bullet in the arsenal of our immune system without it we could not deal with the thousands of rogue cells that turn up in our bodies through our lives."
"Perforin is our body's weapon of cleansing and death," said project leader Professor James Whisstock from Monash University, Melbourne, Australia.
Perforin works by punching holes in cells that have become cancerous or have been invaded by viruses. The holes let toxic enzymes into the cells, which then destroy them.
If perforin isn't working properly the body can't fight infected cells. And there is evidence from mouse studies that defective perforin leads to an upsurge in malignancy, particularly leukaemia, so says Professor Joe Trapani, head of the Cancer Immunology Program at the Peter MacCallum Cancer Centre in Melbourne, Australia.
The first observations that the human immune system could punch holes in target cells was made by the Nobel Laureate Jules Bordet over 110 years ago, but we have had to wait for the latest advances in structural molecular biology to find out how exactly this happens.
Professor Saibil continued "From our previous work we already knew that bacterial toxins, such as the one involved in pneumonia, dramatically change shape to punch holes in membranes. We were fascinated by perforin and wanted to know its structure and how that might change in order for it to act as
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Biotechnology and Biological Sciences Research Council