Scientists at the University of Pennsylvania have determined for the first time the exact structure of the p53 protein, a key molecule in the development of half of cancers derived from patient tissues. Results published in journals ChemBioChem And International Journal of Molecular Sciences.
Also known as the “guardian of the genome,” the p53 protein protects the body’s genome from damage by causing cells to repair DNA or self-destruct. However, mutations in the gene encoding this protein can prevent it from doing its job and cause errors in the genetic code to accumulate, leading to the development of cancer.
The scientists stated that without understanding the entire structure of p53, knowledge of fighting cancer would be incomplete: it is difficult to understand how something works without knowing its physical structure.
The researchers used cryoelectron microscopy (cryo-EM) to visualize individual p53 proteins isolated from patients’ brain tumor cells. The authors used semiconductor materials to capture p53 proteins. These silicon-based microarrays hold proteins in such a way that researchers can see previously unknown features of protein structure.
The researchers looked at seven protein hotspots, which are changes that often lead to the development of cancer. They found that small shifts in the three-dimensional structure of the mutated p53 can affect the surface charges of the protein that needs to interact with DNA. In the future, scientists’ observations will allow for the development of more effective treatments.