Saturday, July 01, 2023

DNA shapes itself to execute new functions as lettuce

Amazing stuff! It is all about atomic-scale lettuce! 😊

"DNA can mimic protein functions by folding into elaborate, three-dimensional structures ...
the researchers used high-resolution imaging techniques to reveal the novel and complex structure of a DNA molecule they created that mimics the activity of a protein called green fluorescent protein (GFP). ...
The findings advance the science of how DNA can be made to fold into complex shapes, and will help researchers build such DNA molecules for a variety of laboratory and clinical applications. ...
Last year, ... discovering one such molecule: a single-stranded DNA that folds in a way that allows it to mimic the activity of GFP. The DNA molecule – which ... dubbed “lettuce” for the color of its fluorescent emissions – works by binding to another small organic molecule, a potentially fluorescent “fluorophore” similar to the one at the heart of GFP, and squeezing it in a way that activates its ability to fluoresce. The researchers demonstrated the lettuce-fluorophore combination as a fluorescent tag for the rapid detection of SARS-CoV-2, the virus that causes COVID-19. ..."

From the abstract:
"Numerous studies have shown how RNA molecules can adopt elaborate three-dimensional (3D) architectures. By contrast, whether DNA can self-assemble into complex 3D folds capable of sophisticated biochemistry, independent of protein or RNA partners, has remained mysterious. Lettuce is an in vitro-evolved DNA molecule that binds and activates conditional fluorophores derived from GFP. To extend previous structural studies of fluorogenic RNAs, GFP and other fluorescent proteins to DNA, we characterize Lettuce–fluorophore complexes by X-ray crystallography and cryogenic electron microscopy. The results reveal that the 53-nucleotide DNA adopts a four-way junction (4WJ) fold. Instead of the canonical L-shaped or H-shaped structures commonly seen in 4WJ RNAs, the four stems of Lettuce form two coaxial stacks that pack co-linearly to form a central G-quadruplex in which the fluorophore binds. This fold is stabilized by stacking, extensive nucleobase hydrogen bonding—including through unusual diagonally stacked bases that bridge successive tiers of the main coaxial stacks of the DNA—and coordination of monovalent and divalent cations. Overall, the structure is more compact than many RNAs of comparable size. Lettuce demonstrates how DNA can form elaborate 3D structures without using RNA-like tertiary interactions and suggests that new principles of nucleic acid organization will be forthcoming from the analysis of complex DNAs."

DNA shapes itself to execute new functions | Cornell Chronicle

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