In a significant advancement for diabetes research, a team from University College London (UCL) has unveiled the crystal structure of an alternative DNA configuration found within the insulin gene. This discovery holds promise for developing targeted therapies for diabetes through a deeper understanding of DNA’s various shapes.
Unveiling Alternative DNA Structures
Published in Nature Communications, the study presents the first crystallographic evidence of i-motif DNA, an alternative structure that diverges from the well-known double helix. While DNA is traditionally depicted as a twisted ladder, researchers have shown that it can adopt multiple configurations, potentially influencing genetic diseases like diabetes and cancer.
Dr. Zoë Waller, co-lead author from UCL’s School of Pharmacy, explained, “Although the double helix is the most recognized form of DNA, alternative structures like the i-motif may play critical roles in genetic conditions.” This i-motif, characterized by a knot-like formation, was first confirmed in human cells in 2018.
Research Insights into the Insulin Gene
The researchers focused on a specific region of the insulin gene capable of folding into various DNA shapes. Dr. Waller noted, “This region exhibits variability among individuals, and our findings indicate that these genetic differences lead to distinct DNA formations.”
To analyze these structures, the team employed advanced crystallography techniques that concentrated DNA solutions to facilitate crystal formation. Dr. Waller highlighted the significance of this method: “We successfully crystallized a four-stranded i-motif DNA structure, allowing us to examine its configuration using X-ray technology. Our results reveal unique interactions within certain DNA sequences that promote the formation of these alternative structures.”
Potential Impacts on Diabetes Treatment and Drug Development
The study demonstrates that variations in the insulin gene sequence can lead to different DNA structures, which may influence the regulation of insulin production. By illustrating the relationship between DNA shape and insulin gene function, crucial for diabetes management, the researchers aim to inform future treatment strategies.
Their findings can aid in computational drug discovery, enabling scientists to target i-motifs in the insulin gene. With knowledge of the specific three-dimensional shapes of these structures, researchers can digitally design molecules that fit precisely, facilitating the rational design of new drugs.
Dr. Waller emphasized the broader implications of their research: “This breakthrough allows us to leverage DNA structure to create molecules that can bind to these configurations, potentially leading to new therapeutic options.”
The research, funded by Diabetes UK, represents a pivotal step forward in the understanding of DNA’s role in disease and underscores UCL’s ongoing commitment to exploring alternative DNA structures, building on previous discoveries such as the G-quadruplex in 2011 and telomere junctions in 2018.
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