Swedish biologists have stabilized the p53 protein, which protects people from cancerous tumors, with the help of spider silk. The results of the study, published in the journal Structure, open up a new avenue for developing cancer vaccines.
Scientists from the Karolinska Institute have found an unusual way to stabilize the p53 protein, which is a cancer suppressor. The researchers attached a small patch of synthetic spider silk protein to human p53. After introduction into the cell, the modified protein begins to be produced in large quantities. It retains the ability to kill cancer cells, but is more stable than p53. Using electron microscopy, computer simulations and mass spectrometry, the scientists showed that parts of spider silk give structure to the disordered regions of the p53 protein.
P53, often referred to as the “guardian of the genome,” plays a key role in protecting the body from cancer. One of the functions of this protein is to prevent genetic mutations that can cause cancer. The absence of functioning p53 in a cell quickly turns it into a cancerous one. Mutations in the p53 gene are found in about half of all tumors, making it the most common genetic change in cancer.
Spider silk is made up of long chains of highly stable proteins and is one of the strongest polymers in nature. For example, synthetic spider silk, produced by bacteria in Fuchzhong Zhang’s laboratory, is stronger than steel and Kevlar.
Michael Landre, one of the authors of the study, says: “The problem is that cells only produce a small amount of p53 and then quickly break it down, because it is a very large and disordered protein. We were inspired by how nature creates stable proteins and decided to use elements of spider silk to stabilize p53.”
Scientists will continue to study the structure of the modified protein. Now we need to determine how different parts of the substance interact with each other to prevent cancer, and to understand how the new p53 modification affects cells and how well they tolerate the built-in components of spider silk.
“Ultimately, we hope to develop an mRNA-based cancer vaccine, but before we do that, we need to find out how the protein is processed in cells, whether a high concentration of the substance would be toxic,” the researchers note.