May 2, 2024

Beyond the Helix: DNA’s Complex Folding Unveils New Functions

” These findings actually change our understanding of what we can do with DNA,” stated study co-author Dr. Samie Jaffrey, Greenberg-Starr Professor of Pharmacology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
DNA in nature exists mostly in a double-stranded, “twisted ladder” or “helical” form, and serves as a reasonably steady store of genetic details. All of the other complicated biological procedures in cells are done by other kinds of molecules, particularly proteins.
In 2015, Dr. Jaffrey and coworkers reported discovering one such molecule: a single-stranded DNA that folds in a method that permits it to mimic the activity of GFP. The DNA molecule, which Dr. Jaffrey dubbed “lettuce” for the color of its fluorescent emissions, works by binding to another small natural particle, a possibly fluorescent “fluorophore” similar to the one at the heart of GFP, and squeezing it in such a way that triggers its capability to fluoresce. The scientists demonstrated the lettuce-fluorophore mix as a fluorescent tag for the quick detection of SARS-CoV-2, the reason for COVID-19.
Dr. Jaffrey and his team discovered lettuce by making numerous single-stranded DNAs and evaluating for those with the desired fluorophore-activating capability. They didnt know what structure lettuce utilized to acquire this capability. To identify that structure, they turned– in the brand-new study– to their long-time collaborator, NHLBI senior detective Dr. Adrian R. Ferré-DAmaré.
In the research study led by Dr. Luiz Passalacqua, a research fellow at Dr. Ferré-DAmarés team, advanced structural imaging strategies were used, including cryo-electron microscopy, to deal with the structure of lettuce at atomic-scale resolution. They found that it folds into a shape that has at its center a four-way junction of DNA, of a type never seen before, enclosing the fluorophore in such a way that triggers it.
They likewise observed that lettuces foldings are held together with bonds between nucleobases– the structure blocks of DNA that are frequently referred to as the “letters” in the four-letter DNA alphabet.
” What we have discovered is not DNA attempting to be like a protein; its a DNA that is doing what GFP does however in its own special way,” said Dr. Ferré-DAmaré.
The scientists stated that the findings should speed the development of fluorescent DNA particles such as lettuce for rapid-diagnostic tests along with a host of other clinical applications in which a DNA-based fluorescent tag is preferable.
” Studies like this are going to be important for the production of brand-new DNA-based tools,” Dr. Jaffrey stated.
Recommendations: “Intricate 3D architecture of a DNA imitate of GFP” by Luiz F. M. Passalacqua, Michael T. Banco, Jared D. Moon, Xing Li, Samie R. Jaffrey and Adrian R. Ferré-DAmaré, 21 June 2023, Nature.DOI: 10.1038/ s41586-023-06229-8.
” Detection of SARS-CoV-2 RNA Using a DNA Aptamer Mimic of Green Fluorescent Protein” by Bria S. VarnBuhler, Jared Moon, Sourav Kumar Dey, Jiahui Wu and Samie R. Jaffrey, 26 March 2023, ACS Chemical Biology.DOI: 10.1021/ acschembio.1 c00893.

This research, which was recently published in the journal Nature, made usage of high-definition imaging technologies to discover the diverse and unique setup of a manufactured DNA particle. Last year, Dr. Jaffrey and associates reported finding one such particle: a single-stranded DNA that folds in a method that enables it to simulate the activity of GFP. The DNA particle, which Dr. Jaffrey dubbed “lettuce” for the color of its fluorescent emissions, works by binding to another little natural particle, a possibly fluorescent “fluorophore” comparable to the one at the heart of GFP, and squeezing it in a method that activates its capability to fluoresce. Dr. Jaffrey and his group discovered lettuce by making many single-stranded DNAs and screening for those with the wanted fluorophore-activating capability.

Illustration revealing the structure of Lettuce, a DNA that binds and activates fluorophores derived from green fluorescent protein. Credit: Luiz F.M. Passalacqua
In a groundbreaking study, scientists from Weill Cornell Medicine and the National Heart, Lung, and Blood Institute, a department of the National Institutes of Health, discovered that DNA can emulate the functions of proteins by forming elaborate, three-dimensional structures.
This research, which was just recently published in the journal Nature, made use of high-definition imaging innovations to discover the complex and unique configuration of a manufactured DNA molecule. This particle was created to imitate the habits of a protein referred to as green fluorescent protein (GFP). Initially drawn out from jellyfish, GFP has actually ended up being a vital tool in labs, acting as a luminous marker or beacon within cells.
The findings advance the science of how DNA can be made to fold into complex shapes, and will help scientists construct such DNA particles for a range of lab and scientific applications. An all-DNA fluorescent tag that simulates GFP, for example, would typically be perfect for labeling targeted pieces of DNA in biological research studies and in diagnostic test sets, and would be relatively inexpensive to make.