A recent study found that spoiled meat is one of the sources for Listeria infections leading to listeriosis. Pregnant women, newborns and immune compromised people are susceptible for a severe progression of this disease. Firstly, the pathogen breaches the intestinal barrier and thus enters the body. The key for further spreading is the invasion protein internalin B that is located on the bacterial surface.

Listeria monocytogenes (Listeria) is a foodborne disease-causing bacterium; the disease is called listeriosis. Listeria can invade the body through a normal and intact gastrointestinal tract. Once in the body, Listeria can travel through the blood stream but Listeria bacteria are often found inside cells. Listeria also produces toxins that damage cells. Image (c) Dennis Kunkel Microscopy, Inc.

On human cells, internalin B activates a receptor molecule called “Met”, thereby signaling the host cell to take up the pathogen. Inside the cell, Listeria uses the host cell’s nutrients and is somehow sheltered from an immune response.

Until now, the researchers did not know how the bacterial invasion protein activates the human receptor. To solve this question, the structural biologists from the HZI first analysed the crystal structures of the single internalin B molecule and of its complex bound to human Met. “In X-Ray structural analysis we noticed that in protein crystals two internalin B molecules align characteristically,” says Hartmut Niemann, assistant professor at the University of Bielefeld. Professor Dirk Heinz, head of the structural biologists at the HZI, explains: “This gave rise to the idea of a dimer – two congregated internalin B molecules – playing a pivotal role in the activation of the Met receptor.”

Minor changes in the internalin B molecule confirmed their hypothesis: inhibiting the congregation of two internalin B molecules prevented the activation of Met. On the other hand, strengthening the interaction resulted in particularly strong receptor activation.

These results may lead to the development of new protein drugs in the future. “Met plays a major role in the body, for example during wound healing,” says Heinz. “Thanks to the extraordinary ability of the internalin B dimer to strongly activate Met, therapeutics for improved wound healing may result someday.”