Abstract
The non-canonical structures of nucleic acids are essential for their diverse functions during various biological processes. These non-canonical structures can undergo conformational exchange among multiple structural states. Data on their dynamics can illustrate conformational transitions that play important roles in folding, stability, and biological function. Here, we discuss several examples of the non-canonical structures of DNA focusing on their dynamic characterization by NMR spectroscopy: (1) G-quadruplex structures and their complexes with target proteins; (2) i-motif structures and their complexes with proteins; (3) triplex structures; (4) left-handed Z-DNAs and their complexes with various Z-DNA binding proteins. This review provides insight into how the dynamic features of non-canonical DNA structures contribute to essential biological processes.
Highlights
Nucleic acids play an important role in all biological processes related to genetic information such as replication, transcription, and translation
According to the base-pair opening kinetics analysis using proton exchange, the lifetime of the innermost C·C+ base-pairs was significantly longer than that of the outer base-pairs. 1D NMR imino proton observation was conducted to identify whether the i-motif lost its tertiary structure due to the formation of G-C base-pairs when presented with G4 in solution
Lee et al investigated supercoiling-induced B–Z transitions at the single-molecule level using single-molecule Förster resonance energy transfer (smFRET) combined with supercoiling-induced B–Z transitions at the single-molecule level using smFRET combined with magnetic tweezers, and suggested that torsion plays an important role in the B-Z transition [122]
Summary
Nucleic acids play an important role in all biological processes related to genetic information such as replication, transcription, and translation. Dynamics studies of protein-nucleic acid interactions are complementary to the complex structures, in that they provide detailed information about the binding interfaces, exchange rates, and conformational changes associated with the binding. The exchange dynamic motions of base-pair opening, the imino protons are useful probes in NMR studies [28,29,30,31,32,33]. The re-equilibration process was monitored by measuring peak intensities in Band-selective Excitation Short-Transient (BEST)-TROSY HSQC [35] spectra after heat shock (Figure 2) These studies demonstrated that the inherent conformational heterogeneities of G4s can be successfully investigated with NMR spectroscopy. Most NMR studies of G4 DNAs routinely monitor imino protons to demonstrate conformational heterogeneity and slow exchange. NMR spectroscopy, and we expect that advances in DNA labeling technology, chemical modification, and NMR techniques will contribute to this field
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