Formation of G‐wires, bimolecular and tetramolecular quadruplex: Cation‐induced structural polymorphs of G‐rich DNA sequence of human SYTX gene

Abstract

An exceptional property of auto-folding into a range of intra- as well as intermolecular quadruplexes by guanine-rich oligomers (GROs) of promoters, telomeres and various other genomic locations is still one of the most attractive areas of research at present times. The main reason for this attention is due to their established in vivo existence and biological relevance. Herein, the structural status of a 20-nt long G-rich sequence with two G5 stretches (SG20) is investigated using various biophysical and biochemical techniques. Bioinformatics analysis suggested the presence of a 17-nt stretch of this SG20 sequence in the intronic region of human SYTX (Synaptotagmin 10) gene. The SYTX gene helps in sensing out the Ca ion, causing its intake in the pre-synaptic neuron. A range of various topologies like bimolecular, tetramolecular and guanine-wires (nano-wires) was exhibited by the studied sequence, as a function of cations (Na /K ) concentration. UV-thermal denaturation, gel electrophoresis, and circular dichroism (CD) spectroscopy showed correlations and established a cation-dependent structural switch. The G-wire formation, in the presence of K , may further be explored for its possible relevance in nano-biotechnological applications.

Polyanion order controls liquid-to-solid phase transition in peptide/nucleic acid co-assembly

“…( Ilc et al, 2013 ; Do et al, 2017 ; Ahmed et al, 2018 ) As shown in Figure 6C , this DNA sequence assembles to give the characteristic CD signature of a parallel GQ. ( Kypr et al, 2009 ; Bhattacharyya et al, 2016 ; Ahmed et al, 2018 ).…”

“…The bimolecular parallel quadruplex-forming DNA, GGTG4TGG, which requires two GQ DNA strands for assembly, organizes to form four stacked guanine quartets with well-ordered charges running along the corners of the GQ planes and potential for extended GQ stacking (Figures 6A,B). (Ilc et al, 2013;Do et al, 2017;Ahmed et al, 2018) As shown in Figure 6C, this DNA sequence assembles to give the characteristic CD signature of a parallel GQ. (Kypr et al, 2009;Bhattacharyya et al, 2016;Ahmed et al, 2018).…”

“…These alterations provided flexibility for chimera-associated quadruplex formation (T4 linker) and enabled peptide-DNA click-conjugation via triazole linkage (Scheme 1). (Hazel et al, 2004;Vondruskova et al, 2008;Do et al, 2017;Ahmed et al, 2018) The click reaction gave rise to the guanine quadruplex Frontiers in Molecular Biosciences frontiersin.org peptide conjugate (GQPC), with linkage between the modified glutamic acid sidechain and the 5′-end of the GQ DNA. To form the quadruplex, two strands of the GQPC chimera must hybridize to give Hoogsteen hydrogen bonds (Figure 6B), forming an intermolecular parallel guanine quadruplex with four quartets and thymine nucleotides present in the loops.…”

Effect of interaction between loop bases and ions on stability of G-quadruplex DNA*

“…[5][6][7][8][9] For example, the formation of G-quadruplex by several G-quartets requires metal ions which dwell in the central of G-quartets are coordinated by several carbonyl oxygen atoms. [10][11][12] The metal ions related in the stability of G-quadruplex including monovalent cations and divalent cations, among which K + and Na + are widely noted since the most physiologically relevant cations, especially K + , placed between G-quartet layers, accepted as one of the most important factor in the stability of G-quadruplex, but little is known about its process of binding in the human telomeric G-quadruplex. [13][14][15] On the other hand, stacked G-quartets form a G4 structure, and the intervening sequences are extruded as single-strand loops, although loops are usually small (1-7 nucleotides (nt)), but the sequence and size of loop have a significant effect on the stability of the G-quadruplex.…”