DNA interacts with several proteins, and these interactions result in structural or functional effects. Protamines, positively charged proteins, can coat negatively charged DNA molecules, packing them into toroids (donut-shaped structures). This process of “condensing” DNA occurs in sperm to densely compact DNA. The exact mechanism of how these proteins bend DNA into toroids is yet unknown. Now, researchers from Amherst College in Massachusetts, USA, have studied this process by using DNA of different lengths. They use atomic force microscopy to visualize the folded DNA structures and a technique called “tethered particle motion” to visualize the folding process.

In their study, the authors found that at low concentrations of protamine (~0.2 µM), the DNA was compacted by ~25% and formed single loops. In some cases, multiple such loops formed a flower-like structure when visualized by using atomic force microscopy. At higher protamine concentrations (³2 µM), they found that the DNA folded into loop stacks with heights and diameters consistent with a series of vertically packed loops. On the basis of their measurements, the authors propose the following model for DNA looping by protamines. An unfolded DNA molecule experiences DNA-DNA interactions and DNA bending in the presence of protamines, creating a single loop or flower intermediate. As more protamine binds to the DNA, the DNA bends more, creating flowers with more loops, eventually collapsing into vertically packed loop stacks.

The authors think that these measurements of DNA folding by protamine would be important not only for studies into packaging of DNA in sperm but also for studies into packaging by condensing agents more broadly, such as in the packaging of viral genomes into a nucleocapsid or in the assembly and folding of DNA origami nanostructures.

Their study titled “Protamine folds DNA into flowers and loop stacks” was published in November 2023 in Biophysical Journal.