Effects of Pressure and pH on the Physical Stability of an I‐Motif DNA Structure

Lepper, Christopher P.; Williams, Martin A. K.; Edwards, Patrick J. B.; Filichev, Vyacheslav V.; Jameson, Geoffrey B.

doi:10.1002/cphc.201900145

Cited by 15 publications

(9 citation statements)

References 53 publications

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“…Because of the small value of the volume change, the stability of i -motifs is nearly insensitive to hydrostatic pressure. In agreement with this expectation, the transition temperatures of the heat-induced i -motif-to-coil transitions do not change or change very weakly with pressure [ 57 , 102 , 103 ]. When treating the volumetric properties of i -motif structures derived from measurements at high pressures, it is important to account for the pressure-induced changes in the pH of the solution, as the stability of an i -motif critically depends on pH.…”

Section: Differential Volume Of Four-stranded and Single-stranded Conformationsmentioning

confidence: 52%

“…Table 5 lists changes in volume, Δ V , measured for heat-induced and pH-induced i -motif-to-coil transitions. In contrast to G-quadruplexes, which are characterized by large negative changes in volume upon unfolding, i -motif-to-single strand transitions exhibit near-zero changes in volume [ 57 , 102 , 103 ]. Because of the small value of the volume change, the stability of i -motifs is nearly insensitive to hydrostatic pressure.…”

Section: Differential Volume Of Four-stranded and Single-stranded Conformationsmentioning

confidence: 99%

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Volumetric Properties of Four-Stranded DNA Structures

Chalikian

Macgregor

2021

Biology

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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.

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Section: Differential Volume Of Four-stranded and Single-stranded Conformationsmentioning

confidence: 52%

Section: Differential Volume Of Four-stranded and Single-stranded Conformationsmentioning

confidence: 99%

Volumetric Properties of Four-Stranded DNA Structures

Chalikian

Macgregor

2021

Biology

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“…Robustness and evolvability may also be modeled computationally using flow reactor simulations (58) . Forms of robustness other than mutational robustness, like the robustness of protein and RNA interaction networks, and robustness to environmental conditions such as temperature (59) , pressure and pH fluctuations (60) can also be explored. The study of the interplay between robustness and evolvability informs our understanding of how new functions evolve in proteins and RNAs (31,(61)(62)(63) , the proposed transition from an RNA world (64) and will help biomolecular engineering of functions under mutational and environmental challenges.…”

Section: Discussionmentioning

confidence: 99%

The genetic robustness of RNA and protein from evolutionary, structural and functional perspectives

Sibaeva

McGimpsey

et al. 2018

Preprint

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The reactions of functional molecules like proteins and RNAs to mutation affect both host cell viability and biomolecular evolution. These molecules are considered robust if function is maintained despite mutations. Proteins and RNAs have different structural and functional characteristics that affect their robustness, and to date, comparisons between them have been theoretical. In this work, we test the relative mutational robustness of RNA and protein pairs using three approaches: evolutionary, structural, and functional. We compare the nucleotide diversities of functional RNAs with those of matched proteins. Across different levels of conservation, we found the nucleotide-level variations between the biomolecules largely overlapped, with proteins generally supporting more variation than matched RNAs. We then directly tested the robustness of the protein and RNA pairs with in vitro and in silico mutagenesis of their respective genes. The in silico experiments showed that proteins and RNAs reacted similarly to point mutations and insertions or deletions, yet proteins are slightly more robust on average than RNAs. In vitro , mutated fluorescent RNAs retained greater levels of function than the proteins. Overall this suggests that proteins and RNAs have remarkably similar degrees of robustness, with the average protein having moderately higher robustness than RNA as a group. Significance StatementThe ability of proteins and non-coding RNAs to maintain function despite mutations in their respective genes is known as mutational robustness. Robustness impacts how molecules maintain and change phenotypes, which has a bearing on the evolution and the origin of life as well as influencing modern biotechnology. Both protein and RNA have mechanisms that allow them to absorb DNA-level changes. Proteins have a redundant genetic code and non-coding RNAs can maintain structure and function through flexible base-pairing possibilities. The few theoretical treatments comparing protein and RNA robustness differ in their conclusions. In this experimental comparison of protein and RNA, we find that they have remarkably similar degrees of overall genetic robustness.

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“…Under favorable solution conditions, G-rich DNA strands fold into a four-stranded G-quadruplex conformation, while C-rich strands adopt a four-stranded i-motif conformation. − There is increasing evidence that noncanonical tetraplex structures, including G-quadruplexes and i-motifs, do exist in the cell and perform important regulatory functions in various genomic events. ,,− To unveil the balance of forces involved in interconversions between duplex and tetraplex structures, the thermal, thermodynamic, and kinetic properties of G-quadruplex and i-motif structures have been extensively studied. ,,− These studies have revealed a complex web of interactions governing transitions between the conformational states available to G-rich and C-rich DNA molecules. ,, On the other hand, volumetric investigations of tetraplex nucleic acid structures are scarce; in fact, the volumetric description of such systems has just begun to emerge. − The volumetric properties of biopolymers provide important insights into the roles of hydration and intramolecular fluctuations in their stability and recognition events which are complementary to insights derived from more conventional structural, calorimetric, and spectroscopic studies. ,,− , …”

Section: Introductionmentioning

confidence: 99%

Volumetric Interplay between the Conformational States Adopted by Guanine-Rich DNA from the c-MYC Promoter

et al. 2021

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The kinetic and thermodynamic stabilities of G-quadruplex structures have been extensively studied. In contrast, systematic investigations of the volumetric properties of G-quadruplexes determining their pressure stability are still relatively scarce. The G-rich strand from the promoter region of the c-MYC oncogene (G-strand) is known to adopt a range of conformational states including the duplex, G-quadruplex, and coil states depending on the presence of the complementary C-rich strand (C-strand) and solution conditions. In this work, we report changes in volume, ΔV, and adiabatic compressibility, ΔK S, accompanying interconversions of G-strand between the G-quadruplex, duplex, and coil conformations in the presence and absence of C-strand. We rationalize these volumetric characteristics in terms of the hydration and intrinsic properties of the DNA in each of the sampled conformational states. We further use our volumetric results in conjunction with the reported data on changes in expansibility, ΔE, and heat capacity, ΔC P, associated with G-quadruplex-to-coil transitions to construct the pressure–temperature phase diagram describing the stability of the G-quadruplex. The phase diagram is elliptic in shape, resembling the classical elliptic phase diagram of a globular protein, and is distinct from the phase diagram for duplex DNA. The observed similarity of the pressure–temperature phase diagrams of G-quadruplexes and globular proteins stems from their shared structural and hydration features that, in turn, result in the similarity of their volumetric properties. To the best of our knowledge, this is the first pressure–temperature stability diagram reported for a G-quadruplex.

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Effects of Pressure and pH on the Physical Stability of an I‐Motif DNA Structure

Cited by 15 publications

References 53 publications

Volumetric Properties of Four-Stranded DNA Structures

Volumetric Properties of Four-Stranded DNA Structures

The genetic robustness of RNA and protein from evolutionary, structural and functional perspectives

Volumetric Interplay between the Conformational States Adopted by Guanine-Rich DNA from the c-MYC Promoter

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