The final step in the process of dealing with a foreign invader is effecting an appropriate lethal response to deal with the threat. The Effector Function theme investigates (a) how our innate immune system responds to the detection of pathogens, and ways to target and modulate the response of specific innate immune cells selectively, and (b) the weaponry associated with immune killing and the roles of complement proteins in immune signalling.
Carnivorous mushrooms reveal human immune trick
Immune cells use a protein punch mechanism to destroy infected cells, cancerous cells, and bacteria—the same trick that edible oyster mushrooms use to consume their prey.
Research by an international team led by the Imaging Centre’s Monash team and Birkbeck College in London has revealed the molecular process behind the ‘hole-punch’ that these organisms use to pass through cell membranes.
The work should open the way to new drug targets and new tools for medicine, agriculture, genetic engineering and nano-engineering.
Using synchrotron light and cryo-electron microscopy, the team took molecular snapshots following the action of an oyster mushroom protein called pleurotolysin. They have been able to observe the hole-punching protein as it latches onto, and puts a hole in, the target cell—either killing the cell directly or providing a passage for other proteins that can kill it.
The team have been able to show the way the protein moves, unfolding and refolding to punch the hole in the target cell. In doing so, they’ve found its Achilles heel. Now they can investigate how to block the hole-punching mechanism, or how to introduce it to new places where this function is desirable.
“The next step is to take what we’ve learned from the mushroom proteins and compare them with equivalent proteins across nature,” says Monash researcher Michelle Dunstone. “Particularly the perforin family of proteins in humans, which we believe will behave in the same way.”
There are potential applications in medicine: dampening immune responses in people with autoimmune disease; stopping listeria escaping our immune cells; and preventing malaria from infecting the liver.
In agriculture these proteins could be introduced into plants and crops, helping them to fight off attacks from pests, and reducing the need for pesticides.
David Fairlie and James Whisstock
Andrew Peele, Julian Vivian, Matt Sweet, Kate Schroder, Helen Saibil, Rodney Tweten, Maciej Markiewski