Insight into tetramolecular DNA G-quadruplexes associated with ALS and FTLDZalar, Matja (Avtor) Wang, Baifan (Avtor) Plavec, Janez (Avtor) Šket, Primož (Avtor) ALSFTLDDNAc9orf7NMRquadruplexcationsThe G$_4$C$_2$ hexanucleotide repeat expansion in the c9orf72 gene is a major genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), with the formation of G-quadruplexes directly linked to the development of these diseases. Cations play a crucial role in the formation and structure of G-quadruplexes. In this study, we investigated the impact of biologically relevant potassium ions on G-quadruplex structures and utilized $^{15}$N-labeled ammonium cations as a substitute for K$^+$ ions to gain further insights into cation binding and exchange dynamics. Through nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we demonstrate that the single d(G$_4$C$_2$) repeat, in the presence of $^{15}$NH$_4{}^+$ ions, adopts a tetramolecular G-quadruplex with an all-syn quartet at the 5′-end. The movement of $^{15}$NH$_4{}^+$ ions through the central channel of the G-quadruplex, as well as to the bulk solution, is governed by the vacant cation binding site, in addition to the all-syn quartet at the 5′-end. Furthermore, the addition of K$^+$ ions to G-quadruplexes folded in the presence of $^{15}$NH$_4{}^+$ ions induces stacking of G-quadruplexes via their 5′-end G-quartets, leading to the formation of stable higher-ordered species.20232024-11-13 15:05:35Članek v reviji164845UDK: 544.1ISSN pri članku: 1422-0067DOI: 10.3390/ijms241713437COBISS_ID: 162931971sl