According to a study conducted by scientists at Weill Cornell Medicine and the National Heart, Lung, and Blood Institute, which is a component of the National Institutes of Health, DNA can fold into intricate, three-dimensional structures in order to imitate the functions that proteins perform.
The novel and intricate structure of a DNA molecule that they created that imitates the activity of a protein known as green fluorescent protein (GFP) was revealed through the use of high-resolution imaging techniques in the study, which was published on June 21 in Nature. GFP, which is derived from jellyfish and acts as a fluorescent tag or beacon in cells, has emerged as an essential tool in the laboratory.
The findings will assist researchers in building such DNA molecules for a variety of laboratory and clinical applications and advance the science of how DNA can fold into complex shapes. For instance, a relatively inexpensive all-DNA fluorescent tag that imitates GFP would be ideal for labeling specific DNA fragments in biological studies and diagnostic test kits.
“What we’ve discovered isn’t DNA attempting to mimic a protein; it’s DNA that does what GFP does but in its own unique way,”
Dr. Ferré-D’Amaré.
“These discoveries truly change how we might interpret how we can manage DNA,” said concentrate on co-creator Dr. Samie Jaffrey, Greenberg-Starr Teacher of Pharmacology and an individual from the Sandra and Edward Meyer Malignant growth Community at Weill Cornell Medication.
In nature, DNA is mostly double-stranded, “twisted ladder” or “helical,” and it stores genetic information in a relatively stable way. Other types of molecules, particularly proteins, carry out all of the other intricate biological processes that take place in cells.
One such molecule was discovered by Dr. Jaffrey and colleagues last year, as reported in ACS Chemical Biology: a DNA with one strand that folds in a way that makes it look like GFP. Due to the color of its fluorescent emissions, the DNA molecule, which Dr. Jaffrey dubbed “lettuce,” functions by squeezing another small organic molecule, a potentially fluorescent “fluorophore” comparable to the one at the heart of GFP, and binding to it. The lettuce-fluorophore combination was used as a fluorescent tag by the researchers to quickly detect COVID-19’s cause, SARS-CoV-2.
By making a lot of single-stranded DNA and looking for those that could activate fluorophores, Dr. Jaffrey and his team found lettuce. However, they had no idea how lettuce acquired this ability. In the new study, they turned to their long-time collaborator, senior investigator Dr. Adrian R. Ferré-D’Amaré, to find that structure.
Advanced structural imaging techniques, such as cryo-electron microscopy, were utilized in the research carried out by Dr. Luiz Passalacqua, a research fellow on Dr. Ferré-D’Amaré’s team, to resolve the structure of lettuce at an atomic-scale resolution. They found that it folds into a shape that has at its middle a four-way intersection of DNA, of a kind never seen, encasing the fluorophore in a way that enacts it. They also noticed that the bonds between nucleobases—the building blocks of DNA that are frequently referred to as the “letters” in the four-letter DNA alphabet—hold the lettuce’s foldings together.
“We have discovered that DNA does not attempt to resemble a protein; According to Dr. Ferré-D’Amaré, “it’s a DNA that is doing what GFP does but in its own unique way.”
The findings, according to the researchers, should accelerate the creation of lettuce-like fluorescent DNA molecules for rapid diagnostic tests and a slew of other scientific applications requiring a DNA-based fluorescent tag.
Dr. Jaffrey stated, “Studies like this are going to be essential for the creation of new DNA-based tools.”
More information: Luiz F. M. Passalacqua et al, Intricate 3D architecture of a DNA mimic of GFP, Nature (2023). DOI: 10.1038/s41586-023-06229-8
