The structure was revealed by combining information about a single perforin molecule visualised using the Australian Synchrotron with Professor Saibil's electron microscope images, (taken in London), of a ring of perforin molecules clustered together to form a hole in a cell membrane.
Professor Whisstock added "Now we know how it works, we can start to fine tune it to fight cancer, malaria and diabetes."
Another interesting finding is that the important parts of the perforin molecule are quite similar to those toxins deployed by bacteria such as anthrax, listeria and streptococcus, showing that this method of making holes in cell membranes is quite ancient in evolution. "The molecular structure has survived for close to two billion years, we think," said Professor Trapani.
Perforin is also the culprit when the wrong cells are marked for elimination, either in autoimmune disease conditions, such as early onset diabetes, or in tissue rejection following bone marrow transplantation. So the researchers are now investigating ways to boost perforin for more effective cancer protection and therapy for acute diseases such as cerebral malaria. And with the help of a 600K grant from the Wellcome Trust they are working on potential inhibitors to suppress perforin and counter tissue rejection.
Professor Douglas Kell, BBSRC Chief Executive said "New technologies in microscopy and synchrotron experiments have opened up tremendous opportunities for molecular biologists. This is a great example where the knowledge we gain about the normal structure and function of a molecule has the potential to underpin important developments in our health and well being."
|Contact: Nancy Mendoza|
Biotechnology and Biological Sciences Research Council