Volumetric Properties of Four-Stranded DNA Structures

Abstract

Four-stranded non-canonical DNA structures including G-quadruplexes and i-motifs have been found in the genome and are thought to be involved in regulation of biological function. These structures have been implicated in telomere biology, genomic instability, and regulation of transcription and translation events. To gain an understanding of the molecular determinants underlying the biological role of four-stranded DNA structures, their biophysical properties have been extensively studied. The limited libraries on volume, expansibility, and compressibility accumulated to date have begun to provide insights into the molecular origins of helix-to-coil and helix-to-helix conformational transitions involving four-stranded DNA structures. In this article, we review the recent progress in volumetric investigations of G-quadruplexes and i-motifs, emphasizing how such data can be used to characterize intra-and intermolecular interactions, including solvation. We describe how volumetric data can be interpreted at the molecular level to yield a better understanding of the role that solute–solvent interactions play in modulating the stability and recognition events of nucleic acids. Taken together, volumetric studies facilitate unveiling the molecular determinants of biological events involving biopolymers, including G-quadruplexes and i-motifs, by providing one more piece to the thermodynamic puzzle describing the energetics of cellular processes in vitro and, by extension, in vivo.

Pressure Perturbation Studies of Noncanonical Viral Nucleic Acid Structures

“…This curvature points toward the possibility of the elliptic boundary, which is typical in case of proteins [16,19,59]. A similar phase diagram has been suggested by Chalikian and Macgregor [22] on the basis of theoretical calculations, but this is the first example, where such curved phase boundary is measured experimentally. Unfortunately, the experimental points cover only a small fraction of the ellipse; therefore, the fitting of the elliptic phase boundary is not possible.…”

“…In experimental practice, pressure is a highly overlooked variable of thermodynamics, although it is equally important as temperature [16][17][18][19][20][21][22]. The low number of high-pressure studies can be partially explained by technical difficulties.…”

“…The usefulness of high-pressure experiments has been proven in a wide range of publications [22][23][24][25][26][27][28][29][30]. According to the Le Chatelier's principle, the pressurized system prefers the state that has the smallest volume.…”

“…Nucleic acids were treated as pressure insensitive for a long time. The unwinding of the double helix structures is hardly influenced by pressure, but noncanonical structures, like GQs and i-motifs show volume changes during their unfolding [22,26,[39][40][41]. Therefore, they are appropriate for such high-pressure studies that can provide volumetric data.…”

Ions in the Deep Subsurface of Earth, Mars, and Icy Moons: Their Effects in Combination with Temperature and Pressure on tRNA–Ligand Binding

“…Generally, water bound to polar and charged groups (such as to phosphates in nucleic acids) occupies a smaller volume with respect to bulk water due to electrostrictive effects (i.e., the contraction of the hydration shell around the biomolecules with densities higher than those of bulk water) [ 53 ]. For example, the unfolding of G-quadruplexes is accompanied by water uptake, which contributes negatively to the overall change in the unfolding volume [ 54 ]. However, consequently, the dehydration process upon binding of the ligand to tRNA should be characterized by a small positive volume change that, in our case, cannot compensate the packing factors contributing to Δ V ° b .…”