Discovery of new protein could revolutionize delivery of anticancer drugs

A previously unknown protein has been discovered in a family of bacteria found in soil and the human gut microbiome that may help deliver drugs to treat cancer.

In a paper published in the journal PNAS, researchers from King’s College London and the University of Washington describe the unique 3D structure of this protein, which is currently being used to develop anti-tumor drug delivery systems that can target drugs to tumor sites.

The bacterial protein identified by the team, which they named BeeR, performs functions similar to actin, the most abundant protein in most human cells. In the presence of a chemical called ATP, actin molecules can link together into long spiral chains called filaments. Filaments are located in the outer membrane of cells and perform many important functions, including helping cells maintain shape, divide, and move. Actin can also break down ATP, which causes filaments to break apart.

Bacteria have actin-like proteins that form filaments in the presence of ATP and help control cell shape and division. But in studying BeeR, the researchers found one striking difference from other actin-like bacterial proteins – its structure.

Dr. Julien Bergeron, senior lecturer at the Randall Centre for Cellular and Molecular Biophysics at King’s College London, who led the study, said: “We used metagenomics data – extensive sequencing of bacterial genomes from the environment – to identify a previously unknown actin-like protein in a family of bacteria known as Verrucomicrobiota. Using the most advanced cryo-electron microscopes, we were able to determine the atomic structure of this protein, showing that instead of a filament, it forms a rigid tube with a cavity in the center.

This strikingly differentiates it from actin or any other bacterial analog.”

Dr. Bergeron first discovered the protein when he was a postdoctoral fellow at the University of Washington School of Medicine in Seattle in the lab of Professor Justin Kollman, the paper’s lead author. But at the time, they were unable to unravel the structure of the protein.

After moving to Queen’s University and studying the protein using advanced imaging techniques, Dr. Bergeron, with the help of lab team members, discovered that in the presence of ATP, BeeR assembles into three struts that form a hollow tubular structure.

“At the moment, we do not know the function of BeeR. Nevertheless, the identification of an actin-like protein that forms a tubular structure changes our understanding of the evolution of this crucial protein family.”

Dr. Julien Bergeron, Senior Lecturer at the Randall Centre for Cellular and Molecular Biophysics at King’s College London

Through his company Prosemble, Dr. Bergeron is working to use the unique hollow tube structure of the BeeR protein to create protein nanoparticles for targeted delivery of anti-tumor drugs to tumor foci. The team is currently testing this approach in preclinical models of breast cancer.

“BeeR structures are not only tubular, but also have a cavity in the center that is large enough to accommodate drug molecules. Because we can easily control the assembly and disassembly of the tube using ATP, this gives us a simple method to deliver and release drugs at the right place,” notes Dr. Bergeron.