Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms19092796
Keywords
i-motif; CCG repeats; trinucleotide repeat DNA; chromomycin A3; neurological disease; X-ray crystallography; nucleotide flip-out; DNA deformation
Funding
- Ministry of Science and Technology, Taiwan [106-2628-M-005-001-MY3]
- Taichung Veterans General Hospital/National Chung Hsing University Joint Research Program [TCVGH-NCHU10776010]
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We have reported the propensity of a DNA sequence containing CCG repeats to form a stable i-motif tetraplex structure in the absence of ligands. Here we show that an i-motif DNA sequence may transition to a base-extruded duplex structure with a GGCC tetranucleotide tract when bound to the (Co-II)-mediated dimer of chromomycin A3, Co-II(Chro)(2). Biophysical experiments reveal that CCG trinucleotide repeats provide favorable binding sites for Co-II(Chro)(2). In addition, water hydration and divalent metal ion (Co-II) interactions also play a crucial role in the stabilization of CCG trinucleotide repeats (TNRs). Our data furnish useful structural information for the design of novel therapeutic strategies to treat neurological diseases caused by repeat expansions.
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