A new study by researchers at Weill Cornell Medicine and the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, found that DNA can fold into complex, three-dimensional structures that mimic the functions of proteins. The study, published on June 21 in Nature, used high-resolution imaging techniques to examine a DNA molecule that mimics the activity of a protein called green fluorescent protein (GFP). GFP is derived from jellyfish and is used in labs as a fluorescent tag or beacon in cells.
DNA in nature exists mostly in a double-stranded, twisted ladder or helical form and stores genetic information. Proteins, on the other hand, carry out the complex biological processes in cells. Last year, Dr. Jaffrey and his colleagues reported discovering a single-stranded DNA, which they called “lettuce” due to the color of its fluorescent emissions, that folds in a way that allows it to mimic the activity of green fluorescent protein (GFP). The DNA molecule works by binding to another small organic molecule, called a fluorophore, similar to the one in GFP, and squeezing it in a way that activates its ability to fluoresce. The lettuce-fluorophore combination was demonstrated by the researchers as a fluorescent tag for the rapid detection of SARS-CoV-2, the cause of COVID-19.
Dr. Jaffrey and his team discovered lettuce by making many single-stranded DNAs and screening for those with the desired fluorophore-activating ability. They didn’t know the structure of lettuce that allowed it to acquire this ability. The team turned to Dr. Adrian R. Ferré-D’Amaré, a long-time collaborator at NHLBI, to help them determine the structure of lettuce.
Dr. Luiz Passalacqua, a research fellow on Dr. Ferré-D’Amaré’s team, led a study that used advanced structural imaging techniques to examine lettuce at an atomic level. The techniques included cryo-electron microscopy. The research team discovered that lettuce folds into a shape that has a four-way junction of DNA at its center. This junction is of a type never seen before. The junction encloses the fluorophore in a way that activates it. The team also observed that bonds between nucleobases hold the foldings of lettuce together. Nucleobases are the building blocks of DNA, often referred to as the “letters” in the four-letter DNA alphabet.
According to Dr. Ferré-D’Amaré, “What we have discovered is not DNA trying to be like a protein; it’s a DNA that is doing what GFP does but in its own special way.”
The researchers believe that these findings could accelerate the development of fluorescent DNA molecules, such as lettuce, for rapid-diagnostic tests. They could also have many other scientific applications in which a DNA-based fluorescent tag is desirable.
Image Credits
In-Article Image Credits
Illustration showing the structure of Lettuce, a DNA that binds and activates fluorophores derived from green fluorescent protein. via Luiz F.M. Passalacqua with usage type - News Release MediaFeatured Image Credit
Illustration showing the structure of Lettuce, a DNA that binds and activates fluorophores derived from green fluorescent protein. via Luiz F.M. Passalacqua with usage type - News Release Media
