Energetic Basis of AGCGA‐Rich DNA Folding into a Tetrahelical Structure

Hadži, San; Kocman, Vojč; Oblak, Domen; Plavec, Janez; Lah, Jurij

doi:10.1002/anie.201813502

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…[1][2][3][4] Two essential parameters define the basic G4 architecture: (1) four strands (G-tracts) with G-residues form G-tetrads via Hoogsteen hydrogen bonding; (2) these G-tetrads stack on each other and recruit monovalent cations (preferably Na + or K + ). This broad and simple definition of G4s can be fulfilled by a variety of different G4 and G4-like [5][6][7] structures (Figure 1I). Restricting and fine-tuning in specific sequences found in the genome, like:…”

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confidence: 99%

Folding dynamics of polymorphic G‐quadruplex structures

Grün

Schwalbe

2021

Biopolymers

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G-quadruplexes (G4), found in numerous places within the human genome, are involved in essential processes of cell regulation. Chromosomal DNA G4s are involved for example, in replication and transcription as first steps of gene expression. Hence, they influence a plethora of downstream processes. G4s possess an intricate structure that differs from canonical B-form DNA. Identical DNA G4 sequences can adopt multiple long-lived conformations, a phenomenon known as G4 polymorphism. A detailed understanding of the molecular mechanisms that drive G4 folding is essential to understand their ambivalent regulatory roles.Disentangling the inherent dynamic and polymorphic nature of G4 structures thus is key to unravel their biological functions and make them amenable as molecular targets in novel therapeutic approaches. We here review recent experimental approaches to monitor G4 folding and discuss structural aspects for possible folding pathways. Substantial progress in the understanding of G4 folding within the recent years now allows drawing comprehensive models of the complex folding energy landscape of G4s that we herein evaluate based on computational and experimental evidence.

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confidence: 99%

Folding dynamics of polymorphic G‐quadruplex structures

Grün

Schwalbe

2021

Biopolymers

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“…The V-coded scaffold (V1131) failed to fold into the desired origami rectangle regardless of folding protocols (Figure 6f and Supplementary Figures 23 and 24), presumably due to the formation of more stable secondary structures for the ssDNA scaffold. AGCGA-quadruplex structures were shown in recent studies as more stable than typical G-quadruplexes without A nucleotides, 44,45 which could explain the difficulties in folding the V coded sequences.…”

Section: ■ Resultsmentioning

confidence: 99%

Expanding DNA Origami Design Freedom with De Novo Synthesized Scaffolds

Wu,

Zhang,

Qin

et al. 2024

J. Am. Chem. Soc.

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The construction of DNA origami nanostructures is heavily dependent on the folding of the scaffold strand, which is typically a single-stranded DNA genome extracted from a bacteriophage (M13). Custom scaffolds can be prepared in a number of methods, but they are not widely accessible to a broad user base in the DNA nanotechnology community. Here, we explored new design and construction possibilities with custom scaffolds prepared in our costand time-efficient production pipeline. According to the pipeline, we de novo produced a variety of scaffolds of specified local and global sequence characteristics and consequent origami constructs of modular arrangement in morphologies and functionalities. Taking advantage of this strategy of template-free scaffold production, we also designed and produced three-letter-coded scaffolds that can fold into designated morphologies rapidly at room temperature. The expanded design and construction freedom immediately brings in many new research opportunities and invites many more on the horizon.

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“…Oligonucleotide VK2, 5′‐d(G 3 AGCGAG 3 AGCGAG 3 AGCGA G 3 AGCG)‐3′, originating from regulatory region of the PLEKHG3 human gene, related to autism, is a representative member of the AGCGA‐quadruplex family . VK2 adopts a monomeric structure with a C 2 axis of symmetry (Figures ; Figure S1, Supporting Information) . Intriguingly, its sequence adheres to folding motifs required for both G‐ and AGCGA‐quadruplexes.…”

Section: Figurementioning

confidence: 94%

“…Therefore, in the complex compared to VK2 alone the hydrophobic core of G9–G11, G10–G10 and G11–G9 base pairs around two A8 residues is extended with a GAGA‐ and two GCGC‐quartets. Although the conformational freedom in the center of VK2 alone is a major source of the entropic contribution to the stability of the structure, we postulate that the VK2–360 complex is stabilized in the center by a hydrophobic core and entropically by conformational freedom of G1–G3, G2–G2, G3–G1 and two A4–G15 base pairs on top of the complex (Figures S11 and S12, Supporting Information).…”

Section: Figurementioning

confidence: 99%

Intercalation of a Heterocyclic Ligand between Quartets in a G‐Rich Tetrahelical Structure

Kotar

Kocman

Plavec

2020

Chemistry A European J

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YES G-rich oligonucleotide VK2 folds into an AGCGA-quadruplex tetrahelical structure distinct ands ignificantly differentf rom G-quadruplexes, even thoughi t contains four G 3 tracts. Herein, ab is-quinoliniuml igand 360A with high affinity for G-quadruplex structures and selective telomerase inhibition is shown to strongly bind to VK2. Upon binding, 360A does not induce ac onformational switch from VK2 to an expected G-quadruplex. In contrast, NMR structural study revealed formation of a well-definedV K2-360A complex with a1 :1 binding stoichiometry,i nw hich3 60A intercalates between GAGA-a nd GCGC-quartets in the central cavity of VK2. This is the first high-resolution structure of aG -quadruplex ligand intercalating into aG -rich tetrahelical fold. This unique mode of ligand binding into tetrahelical DNA architecture offers insights into the stabilization of an AGCGA-quadruplexb ya heterocyclic ligand and provides guidelines for rational design of novel VK2 bindingm olecules with selectivity for different DNA secondary structures.

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Energetic Basis of AGCGA‐Rich DNA Folding into a Tetrahelical Structure

Cited by 9 publications

References 37 publications

Folding dynamics of polymorphic G‐quadruplex structures

Folding dynamics of polymorphic G‐quadruplex structures

Expanding DNA Origami Design Freedom with De Novo Synthesized Scaffolds

Intercalation of a Heterocyclic Ligand between Quartets in a G‐Rich Tetrahelical Structure

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