In order to protect us from disease, our immune cells use proteins to punch their way into harmful cells and destroy them. Now, a new study has captured how a carnivorous mushroom engages in a similar process, allowing it to kill parasites. Researchers say visualizing this process brings us closer to understanding how it works in humans, potentially opening the door to new treatments for autoimmune diseases and other conditions.
The research team – co-led by Dr. Michelle Dunstone of Monash University in Melbourne, Australia, and Prof. Helen Saibil of Birbeck College in the UK – publishes their findings in the journal PLOS Biology.
According to the background of the study, animals, plants, fungi and bacteria all use proteins to smash holes, or “pores,” into harmful cells and kill them.
“These proteins are able to insert into the plasma membranes of target cells, creating large pores that short circuit the natural separation between the intracellular and extracellular milieu, with catastrophic results,” the authors explain.
Exactly how the proteins do this, however, has been unclear. In their study, the team set out to determine the hole-punching process behind a protein called pleurotolysin, found in the edible oyster mushroom, also known as the Pleurotus ostreatus.
The oyster mushroom most commonly grows on trees and helps decompose deciduous types. It is a carnivorous mushroom; it feeds off parasites called nematodes, or roundworms.
Using both X-ray crystallography and cryo-electron microscopy, the researchers were able to capture the way in which pleurotolysin moves to stab its way through parasites. They found the protein repeatedly folds and unfolds to punch holes in its target and kill it.
“I never believed I’d be able to see these proteins in action,” says Dr. Dunstone. “It’s an amazing mechanism, and also amazing that we now have the technology to see these hole-punching proteins at work.”
The video below shows the pleurotolysin protein in action:
By uncovering the mechanism behind the protein’s hold-punching technique, the researchers say it gives them ground to find ways to block this process or direct it to areas where it is required.
The team says they believe a protein found in humans – called perforin – will behave the same way as pleurotolysin to kill its target cell, and if so, it could open to door to new therapies or prevention strategies for an array of diseases.
For example, they say the technique could be used to reduce immune response in individuals with autoimmune diseases or to stop malaria from infecting the liver.
In addition, the hole-punching technique could be applied to agriculture. The team says it could be used in crops and plants to help them ward off pests, which could lower the need for pesticides.
Commenting on their findings, Prof. Saibil says:
“We still have a lot of work to do before our ideas reach the clinic or industry, but seeing how the machinery works is an important step forward.”