The secrets of a molecular assassin could lead to more effective treatments for cancer and viral diseases, better therapy for autoimmune conditions, and a deeper understanding of the body’s defences enabling the development of more tightly focused immunosuppressive drugs.
These are just some of the wide-ranging possibilities arising from research which has revealed the structure and function of the protein perforin, a front-line weapon in the body’s fight against rogue cells.
A pivotal role was played by 2006 Science Minister’s Life Scientist of the Year, molecular biologist Prof James Whisstock and his research team at Monash University. It was research fellow Dr Ruby Law who finally worked out how to grow crystals of perforin. And the team was then able to collaborate with Dr Tom Caradoc-Davies of the micro-crystallography beamline at the nearby Australian Synchrotron to reveal its complete molecular structure.
When they put their information together with that of colleagues at the Peter MacCallum Cancer Centre in Melbourne, and Birkbeck College in London, they found they could puzzle out the way the molecule functions to punch holes in the outer membranes of cells invaded by viruses. The immune system then uses these pores as access points for packages of toxic enzymes which kill off the infected cells. The process prevents the replication and spread of virus particles within the body.
“This is a weapon of cleansing and death,” James says. “It’s the body’s key tool for killing off rogue cells, and an essential part of the immune system.” The work, published in Nature late last year, is also a dramatic illustration of the importance of the Australian Synchrotron, he said.
Photo: In this simulation, the perforin molecule (blue) punches a hole through the cell membrane (beige) providing access for toxic enzymes (red)
Credit: Mike Kuiper
Department of Biochemistry and Molecular Biology, Monash University, James Whisstock, James.Whisstock@monash.edu, www.med.monash.edu.au/biochem/staff/whisstock.html