Scientists have decoded the molecular mechanism of a fish toxin that may have great therapeutic potential in cancer treatment.
The Yersinia species of pathogens can cause the bubonic plague and serious gastrointestinal infections in humans.
Thomas Jank and his fellow researchers at the University of Freiburg in Germany studied a pathogen of the Yersinia family (Yersinia ruckeri).
This pathogen causes redmouth disease in Salmonidae, a family of ray-finned fish which includes salmon and trout.
The researchers were able to identify a toxin injection machine in the Y ruckeri genome.
The group demonstrated that the toxin Afp18 in this injection machine is an enzyme that deactivates the switch protein RhoA, which is responsible for many vital processes in the cells of humans and fish.
RhoA controls the building up and breaking down of actin filaments, which are not only necessary for cell division, but also for the spreading of tumour metastases in the body.
In close collaboration with the developmental biologist Wolfgang Driever, also from the University of Freiburg, the research group injected the toxin Afp18 into zebra fish embryos.
The result was that cell division was blocked, and the fish embryos did not develop. The toxin caused the actin filaments in the fish cells to collapse.
This is because the Afp18 attaches a sugar molecule, an N-acetylglucosamine, onto the amino acid tyrosine in RhoA.
According to the scientists, this is a very unusual reaction in nature. The team was able to shed light on this mechanism at the atomic level through the X-ray analysis of Afp18-modified RhoA crystals.
For this, they collaborated with Daan von Aalten from the University of Dundee, Scotland. Rho-regulatory proteins are involved in the growth of cancer, especially metastasis.
Thus, the researchers believe that this fish toxin has great therapeutic potential in cancer treatment.
The study was published in the journal Nature Communications.
