Spider silk is an incredibly strong and flexible material ( it is stronger than steel and Kevlar, and can stretch up to four times its length before breaking), and now a team of scientists from Karolinska Institutet (KI) in Sweden has discovered another use for this amazing material from nature: to stabilize and enhance p53, a protein that suppresses cancer.
A very versatile material
The p53 protein is responsible for protecting our cells against cancer , hence it is known as “guardian of the genome” ; regulates the expression of a large number of genes, including the PIG3 gene, which are involved in stopping cell division, DNA repair and apoptosis or programmed cell death, that is, this protein essentially monitors cell division and stops it if it detects DNA damage or a mutation (this prevents damaged cells from becoming cancerous). In about half of all cancerous tumors, mutations of the p53 gene are found. The problem with this protein is that it breaks down quickly in the cell.
The researchers decided to add synthetic spider silk to p53 , finding that it made it more stable and more potent, effectively demonstrating that it is feasible to develop a protein capable of destroying cancer cells.
“The problem is that cells only produce small amounts of p53 and then quickly break it down, as it is a very large and messy protein,” explains Michael Landreh, a researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet and co-author. from work. “We have been inspired by how nature creates stable proteins and have used spider silk protein to stabilize p53. Spider silk consists of long chains of highly stable proteins and is one of nature’s strongest polymers.”
The new protein proved to be not only more stable than ordinary p53, but also more capable of killing cancer cells.
The study, which was published in the journal Structure , therefore shows that the addition of spider silk could prevent it from breaking down so quickly in the cell and potentially increase its ability to kill cancer cells. The team believes that if this is improved further, the spider silk protein could be a possible candidate for a future mRNA vaccine.
“Creating a more stable variant of p53 in cells is a promising approach for cancer therapy, and now we have a tool for this that is worth exploring,” says study co-author David Lane. “Eventually we hope to develop an mRNA-based cancer vaccine , but before we do that we need to know how the protein is handled in cells and whether large amounts can be toxic.”
Using a combination of electron microscopy, computer simulations and mass spectrometry, the researchers were able to delve into the reasons why adding spider silk to the protein has these effects, although further study is needed to support the hypothesis. greater structure to the disordered sections within the main protein.
The authors explain that they did not test whether their improved protein actually had an effect on tumor suppression, they only identified that it was stable and biologically active. Future studies will examine how this protein interacts with other proteins to prevent cancer, as well as whether spider silk could cause any additional health problems.
Margit Kaldmäe, Thibault Vosselman, et al. A “spindle and thread” mechanism unblocks p53 translation by modulating N-terminal disorder. Structure , 2022; DOI: 10.1016/j.str.2022.02.013