The role of loops and cation on the volume of unfolding of G-quadruplexes related to HTel

Li, Yang Yun; Dubins, David N.; Le, Dianna My Nhi Thi; Leung, Karen Ka Yan; Macgregor, Robert B.

doi:10.1016/j.bpc.2016.12.003

Cited by 19 publications

(34 citation statements)

References 35 publications

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“…A later study, which included several loop mutants of Htel, resulted in slightly smaller molar volume changes with both sodium and potassium ions upon unfolding of the GQ [37]. Potassium-stabilized GQs had smaller volume, which corresponds well with the higher stability of the K þ containing GQs.…”

Section: Resultsmentioning

confidence: 86%

“…Potassium-stabilized GQs had smaller volume, which corresponds well with the higher stability of the K þ containing GQs. -12 cm 3 /mol out of the -43 cm 3 /mol volume change was associated to the re-solvation of the potassium ions [37].…”

Section: Resultsmentioning

confidence: 94%

“…The increased density and consequently the reduced volume of this solvent layer appears as a negative contribution to the volume of the solute molecule. In the case of proteins, this hydration layer increases upon unfolding [24,25,26], while in the case of GQs, the hydration shell of the released ions may also play a role [27].…”

Section: Volumetric Effectsmentioning

confidence: 99%

See 2 more Smart Citations

Negative volume changes of human G-quadruplexes at unfolding

Molnár

Somkuti

Smeller

2020

Heliyon

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G-quadruplexes are tetrahelical structures. They are important targets for anti-cancer drugs, since they are situated at crucial positions within the genome. We studied the volumetric properties of the unfolding of three G-quadruplexes in the presence of potassium ion. The unfolding volume changes were determined using high-pressure fluorescence spectroscopy. The c-MYC, KIT, and VEGF sequences unfold with the transition volume of -17, -6 and -18 cm 3 /mol, respectively. The small magnitude of the unfolding volume of KIT could be explained by its unique structure and the lower amount of void volume. Since the cell interior is highly crowded, the available volume is restricted. Therefore the volumetric changes during the conformational transformations gain biological importance.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 94%

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Negative volume changes of human G-quadruplexes at unfolding

Molnár

Somkuti

Smeller

2020

Heliyon

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“…Table 1 presents a compilation of literature data on changes in volume accompanying unfolding transitions of G-quadruplexes differing in topology and sequence. Inspection of Table 1 reveals that G-quadruplex-to-single strand transitions are accompanied by negative changes in volume, Δ V [ 48 , 92 , 93 , 94 , 95 , 96 , 97 ]. To rationalize a change in volume accompanying G-quadruplex unfolding, one needs to carefully consider the entire set of molecular interactions that may contribute to the change.…”

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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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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“…G-quadruplexes (G4s) are special nucleic acid secondary structures formed by tandem repetitive G-rich DNA/RNA sequences [1][2][3]. In accordance with its preferential localization in functional genomic regions, G4 plays very important regulatory roles in telomere length maintenance, gene replication, transcription, and translation processes [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Quantitative and real-time measurement of helicase-mediated intra-stranded G4 unfolding in bulk fluorescence stopped-flow assays

Liu

Guo

et al. 2020

Anal Bioanal Chem

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G-Quadruplexes (G4s) are thermodynamically stable, compact, and poorly hydrated structures that pose a potent obstacle for chromosome replication and gene expression, and requiring resolution by helicases in a cell. Bulk stopped-flow fluorescence assays have provided many mechanistic insights into helicase-mediated duplex DNA unwinding. However, to date, detailed studies on intramolecular G-quadruplexes similar or comparable with those used for studying duplex DNA are still lacking. Here, we describe a method for the direct and quantitative measurement of helicase-mediated intramolecular G-quadruplex unfolding in real time. We designed a series of site-specific fluorescently double-labeled intramolecular G4s and screened appropriate substrates to characterize the helicase-mediated G4 unfolding. With the developed method, we determined, for the first time to our best knowledge, the unfolding and refolding constant of G4 (≈ 5 s −1), and other relative parameters under single-turnover experimental conditions in the presence of G4 traps. Our approach not only provides a new paradigm for characterizing helicasemediated intramolecular G4 unfolding using stopped-flow assays but also offers a way to screen for inhibitors of G4 unfolding helicases as therapeutic drug targets.

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The role of loops and cation on the volume of unfolding of G-quadruplexes related to HTel

Cited by 19 publications

References 35 publications

Negative volume changes of human G-quadruplexes at unfolding

Negative volume changes of human G-quadruplexes at unfolding

Volumetric Properties of Four-Stranded DNA Structures

Quantitative and real-time measurement of helicase-mediated intra-stranded G4 unfolding in bulk fluorescence stopped-flow assays

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