Insight into tetramolecular DNA G-quadruplexes associated with ALS and FTLD : cation interactions and formation of higher-ordered structure

Zalar, Matja (avtor), Wang, Baifan (avtor), Plavec, Janez (avtor), Šket, Primož (avtor)

The 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.

• Jezik: Angleški jezik
• Ključne besede: ALS, FTLD, DNA, c9orf7, NMR, quadruplex, cations
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 19 str.
• Številčenje: Vol. 24, iss. 17, art. 13437
• PID: 20.500.12556/RUL-164845
• UDK: 544.1
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms241713437
• COBISS.SI-ID: 162931971
• Datum objave v RUL: 13.11.2024

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, tetramolekule, kationi, kvadrupleksi, DNK, amiotrofična lateralna skleroza