Scientists at the University of College London have made a groundbreaking discovery, revealing the first crystal structure of an alternative DNA shape from the insulin gene. This breakthrough could lead to new insights into diabetes treatment.
DNA is typically formed of two strands that wind around each other, known as a double helix. However, researchers have long suspected that alternative DNA structures exist and may play a role in genetic diseases such as diabetes or cancer.
The study, published in Nature Communications, focuses on i-motif DNA, which has an interlocking structure resembling a knot. This type of DNA was only confirmed to be found in living human cells in 2018.
The researchers used a crystallography technique to concentrate the solution containing the DNA, allowing crystals to form and enabling them to determine the exact structure of this DNA using X-ray crystallography.
The findings show that different sequence variants in the insulin gene form different DNA structures, which could affect whether insulin is switched on or off. This knowledge can guide future research into diabetes treatment.
Moreover, the crystal structure developed by the scientists enables computational-based drug discovery to target the i-motifs from the insulin gene. This process, called rational design, allows researchers to design molecules digitally and model them to see if they will fit the drug target best.
The study’s lead author, Dr. Zoë Waller, notes that this research means that now scientists can use the shape of DNA to design molecules to bind these structures, which could be developed into drugs and potentially medicines. The findings also provide a model for other targets in the genome that form this shape of DNA, besides the insulin gene.
Source: https://phys.org/news/2024-09-crystallized-alternative-dna-insulin-diabetes.html