14 DAY TRIAL // The results of a new scientific study are now forcing experts to rethink the way they look at DNA. For a long time, the acid was believed to be only a “passive blueprint” that produces proteins, but now its role appears to be a tad more active.
Deoxyribonucleic acid (DNA) produces molecules known as proteins through a mechanism called RNA transcription. Experts thought that this is what the role of the genetic material was, but it now turns out that DNA also plays a role in fine-tuning the activity on nuclear receptors.
These special proteins play a critical part in underlying cells' sensibility to steroid and thyroid hormones. They also bind to other types of molecules, say investigators from the Scripps Research Institute (SRI) Florida campus.
“There is an elaborate biochemical dialogue going on between the receptor, ligand, coregulatory proteins, and the specific DNA sequence that the nuclear receptor complex is bound to,” SRI researcher Patrick R. Griffin, PhD, explains.
“But until this study, it was not completely clear what the structural basis for this crosstalk was,” adds the investigator, who is the director of the Translational Research Institute at Scripps Florida. He is also the chair of the SRI Department of Molecular Therapeutics.
The new discovery could have tremendous health benefits, and could directly lead to the development of new therapies aimed at conditions including osteoporosis, obesity, autoimmune disease, and cancer.
According to investigators, these treatments would rely on the activation of specific genes in well-timed sequences. Gaining the ability to do so selectively is something researchers have been working on for many years.
Using an investigations technique called hydrogen-deuterium exchange (HDX) mass spectrometry, SRI scientists looked at the interactions between a protein complex comprising the vitamin D receptor and the retinoic X receptor and their ligands.
They also investigated how DNA, co-regulatory proteins (including steroid receptor coactivator 1), vitamin D and a metabolite of vitamin A called 9-cis-retinoic acid fit into the picture.
“HDX mass spectrometry is a high-precision, high-sensitivity mapping technique. With it, we can find the specific regions of the protein complex that are altered upon interaction with ligand,” Griffin says.
“This information can be used to infer structural changes that are the result of a specific interaction,” the expert goes on to say, quoted by Daily Galaxy.
One of the most important discoveries was that DNA can use long-range structural effects to alter the structure and function of protein complexes. This is the first time that this is demonstrated to happen with such a high degree of spatial resolution as the one HDX mass spectrometry allows.