8X4F
Solution NMR structure of a DNA hairpin formed by pure CTG repeats
Summary for 8X4F
| Entry DOI | 10.2210/pdb8x4f/pdb |
| Descriptor | DNA (5'-D(*GP*CP*TP*GP*CP*TP*GP*CP*TP*GP*CP*TP*GP*C)-3'), SODIUM ION (2 entities in total) |
| Functional Keywords | hairpin, ctg repeat expansion, myotonic dystrophy type 1, dna |
| Biological source | Homo sapiens |
| Total number of polymer chains | 1 |
| Total formula weight | 4562.62 |
| Authors | |
| Primary citation | Wan, L.,He, A.,Li, J.,Guo, P.,Han, D. High-Resolution NMR Structures of Intrastrand Hairpins Formed by CTG Trinucleotide Repeats. Acs Chem Neurosci, 15:868-876, 2024 Cited by PubMed Abstract: The CAG and CTG trinucleotide repeat expansions cause more than 10 human neurodegenerative diseases. Intrastrand hairpins formed by trinucleotide repeats contribute to repeat expansions, establishing them as potential drug targets. High-resolution structural determination of CAG and CTG hairpins poses as a long-standing goal to aid drug development, yet it has not been realized due to the intrinsic conformational flexibility of repetitive sequences. We herein investigate the solution structures of CTG hairpins using nuclear magnetic resonance (NMR) spectroscopy and found that four CTG repeats with a clamping G-C base pair was able to form a stable hairpin structure. We determine the first solution NMR structure of dG(CTG)C hairpin and decipher a type I folding geometry of the TGCT tetraloop, wherein the two thymine residues form a T·T loop-closing base pair and the first three loop residues continuously stack. We further reveal that the CTG hairpin can be bound and stabilized by a small-molecule ligand, and the binding interferes with replication of a DNA template containing CTG repeats. Our determined high-resolution structures lay an important foundation for studying molecular interactions between native CTG hairpins and ligands, and benefit drug development for trinucleotide repeat expansion diseases. PubMed: 38319692DOI: 10.1021/acschemneuro.3c00769 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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