New Insights Into the Antibacterial Function of GBP1 Proteins

The protein GBP1 is an essential part of the human body's defense mechanism against infections. However, the mechanism by which this material envelops germs and parasites in a protein sheath to combat them has not yet been discovered.

Now, scientists at Delft University of Technology have figured out how this protein works. Published in the journal Nature Structural & Molecular Biology, this new information may help create drugs and treatments for people with compromised immune systems.

GBPs form the first line of defense against various infectious diseases caused by bacteria and parasites. Examples of such diseases include dysentery, typhoid fever caused by Salmonella bacteria, and tuberculosis. The protein also plays a significant role in the sexually transmitted infection chlamydia as well as in toxoplasmosis, which is particularly dangerous during pregnancy and for unborn children.”

Arjen Jakobi, Biophysicist, Delft University of Technology

Coat Around Bacteria

In their study, Jakobi and his associates explain for the first time how the innate immune system uses GBP1 proteins to combat germs.  

The protein surrounds bacteria by forming a sort of coat around them. By pulling this coat tighter, it breaks the membrane of the bacteria the protective layer surrounding the intruder after which immune cells can clear the infection.”

Tanja Kuhm, PhD Candidate and Study Lead Author, Delft University of Technology

Deciphering the Defense Strategy

Using a cryogenic electron microscope, the researchers investigated the binding of GBP1 proteins to bacterial membranes to decipher the defense mechanism of GBPs; because of this, they were able to see the process in amazing detail, even down to the molecular level.

We were able to obtain a detailed three-dimensional image of how the protein coat forms. Together with biophysical experiments conducted in Sander Tans’ research group at research institute AMOLF, which enabled us to manipulate the system precisely, we succeeded in deciphering the mechanism of the antibacterial function.”

Arjen Jakobi, Biophysicist, Delft University of Technology

Medications

According to Jakobi, this study advances the knowledge of how the body fights off bacterial infections. “If we can grasp this well, and we can specifically activate or deactivate the involved proteins through medication, it may offer opportunities to speed up getting rid of certain infections,” Jakobi concludes.