7ZYX

Dimeric i-motif from 2'Farabinocytidine-modified TC5

Summary for 7ZYX

• Entry DOI: 10.2210/pdb7zyx/pdb
• NMR Information: BMRB: 34735
• Descriptor: DNA (5'-D(*TP*(CFL)P*(CFL)P*(CFL)P*(CFL)P*(CFL))-3') (1 entity in total)
• Functional Keywords: i-motif, fana, 2'farabinocytidine, dna
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 3590.20

Authors

Garavis, M.,El Khoury, R.,Damha, M.J.,Gonzalez, C. (deposition date: 2022-05-25, release date: 2023-03-01, Last modification date: 2024-06-19)

Primary citation

El-Khoury, R.,Macaluso, V.,Hennecker, C.,Mittermaier, A.K.,Orozco, M.,Gonzalez, C.,Garavis, M.,Damha, M.J.
i-Motif folding intermediates with zero-nucleotide loops are trapped by 2'-fluoroarabinocytidine via F···H and O···H hydrogen bonds.
Commun Chem, 6:31-31, 2023

PubMed Abstract: G-quadruplex and i-motif nucleic acid structures are believed to fold through kinetic partitioning mechanisms. Such mechanisms explain the structural heterogeneity of G-quadruplex metastable intermediates which have been extensively reported. On the other hand, i-motif folding is regarded as predictable, and research on alternative i-motif folds is limited. While TC normally folds into a stable tetrameric i-motif in solution, we report that 2'-deoxy-2'-fluoroarabinocytidine (araF-C) substitutions can prompt TC to form an off-pathway and kinetically-trapped dimeric i-motif, thereby expanding the scope of i-motif folding landscapes. This i-motif is formed by two strands, associated head-to-head, and featuring zero-nucleotide loops which have not been previously observed. Through spectroscopic and computational analyses, we also establish that the dimeric i-motif is stabilized by fluorine and non-fluorine hydrogen bonds, thereby explaining the superlative stability of araF-C modified i-motifs. Comparative experimental findings suggest that the strength of these interactions depends on the flexible sugar pucker adopted by the araF-C residue. Overall, the findings reported here provide a new role for i-motifs in nanotechnology and also pose the question of whether unprecedented i-motif folds may exist in vivo.

PubMed: 36797370
DOI: 10.1038/s42004-023-00831-7

Experimental method

SOLUTION NMR