Helen Saibil on our immune system’s killer protein

Our immune system uses a tiny protein called perforin to punch holes in the membranes of infected cells, says an October, 2010 report.

The human immune system keeps us well by attacking and killing the cells that make us sick, a team of researchers announced in October 2010. The key is a tiny protein called perforin. It punches holes in the membranes of infected cells and then fills them with toxic enzymes.

Helen Saibil: The protein is perforin. It’s a very important weapon of the immune system against cells in our blood stream that are infected by viruses or are cancerous.

Helen Saibil, of Birkbeck College, London, is a biologist and a co-author of the study. Her team used a powerful microscope to watch as perforin punched holes in the membrane of an infected cell. She described how a type of white blood cell called “natural killer cells” use perforin as a weapon.

Helen Saibil: It makes a very tight and small contact with the cell it’s going to kill. And then it releases these bags, with the perforin and the toxic enzyme, into a little space between two cells. Then the perforin is released just in a spot where it’s about to make a hole in the cell that’s going to be killed.

Now that scientists know how the protein is shaped and how it works, the knowledge could be used to design new types of drugs that act on perforin, Saibil said.

Helen Saibil: We can think about how to design drugs that would slow it down if it’s too active, or speed it up if it’s not active enough.

She said that could mean new treatments for cancer, malaria, and autoimmune diseases. The study, published in the journal Nature, is the culmination of a 10-year collaboration between Saibil’s team in London, and a team of scientists in Melbourne, Australia.

Helen Saibil: Until now we didn’t know the three-dimensional shape of this molecule, or how it actually does the hole punching. We’re very interested in basic biological mechanisms, how protein machines do their jobs in our bodies. Our Australian collaborators found out what the molecule’s shape is in detail, and we found out what it looks like when it assembles into these pores, into the holes in the target cell membrane.

Saibil said that perforin – so named for its ability to “perforate” cells – actually changes shape as it does its job.

Helen Saibil: A part of the protein structure actually comes out, unfolds, and unravels, and makes the wall of what’s going to be the pore.

This action of perforin is essential to our survival, Saibil said.

Helen Saibil: We’re constantly bombarded with things like [infections] from our environment, and mistakes are made in our cells. Our cells become cancerous, and our immune system tries to get rid of anything like that. So we really need this for immune surveillance throughout our lives. If we don’t have it, it’s very bad news.

Without perforin, Saibil said, our bodies can’t fight off cancers and viruses. People who are born with a genetic defect in perforin do not typically survive long. On the other hand, if your perforin is over-active, it means you have an autoimmune disease – the immune system is too active, and it uses perforin to attack healthy cells in addition to bad cells.

Lindsay Patterson