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Review
. 2016 Sep 9:4:38.
doi: 10.3389/fchem.2016.00038. eCollection 2016.

Metal Cations in G-Quadruplex Folding and Stability

Debmalya Bhattacharyya  1 , Gayan Mirihana Arachchilage  1 , Soumitra Basu  1
Affiliations
Review

Metal Cations in G-Quadruplex Folding and Stability

Debmalya Bhattacharyya et al. Front Chem. .

Abstract

This review is focused on the structural and physicochemical aspects of metal cation coordination to G-Quadruplexes (GQ) and their effects on GQ stability and conformation. G-quadruplex structures are non-canonical secondary structures formed by both DNA and RNA. G-quadruplexes regulate a wide range of important biochemical processes. Besides the sequence requirements, the coordination of monovalent cations in the GQ is essential for its formation and determines the stability and polymorphism of GQ structures. The nature, location, and dynamics of the cation coordination and their impact on the overall GQ stability are dependent on several factors such as the ionic radii, hydration energy, and the bonding strength to the O6 of guanines. The intracellular monovalent cation concentration and the localized ion concentrations determine the formation of GQs and can potentially dictate their regulatory roles. A wide range of biochemical and biophysical studies on an array of GQ enabling sequences have generated at a minimum the knowledge base that allows us to often predict the stability of GQs in the presence of the physiologically relevant metal ions, however, prediction of conformation of such GQs is still out of the realm.

Keywords: DNA; G-quadruplex; RNA; metal ion coordination; polymorphism; stability; structure.

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Figures

Figure 1
Figure 1
Cellular processes influenced and modulated by RNA and DNA G-quadruplex structures.
Figure 2
Figure 2
Chemical structure of a G-quartet. Four guanosines are hydrogen bonded (green dashes) by Hoogsteen base pairings and the monovalent cation K+ interacts with O6 atoms (in red).
Figure 3
Figure 3
Different topological variants of G-quadruplexes. (A) Intramolecular antiparallel 3-tiered GQ; (B) Intramolecular antiparallel 2-tiered GQ; (C) Intramolecular parallel 3-tiered GQ; (D) Bimolecular antiparallel 3-tiered and (E) Tetramolecular antiparallel 3-tiered GQ.
Figure 4
Figure 4
Structure of the Oxytricha nova telomeric DNA d(GGGGTTTTGGGG) in the presence of different monovalent cations. The side views of the crystal structure in the presence of K+ (A), Na+ (D) and Tl+ (G) ions. A view shown down the central ion channel of the quadruplex in the presence of K+ (B), Na+ (E) and Tl+ (H). Schematic representations of the bi-molecular quadruplex showing positions of the monovalent cations in the central ion channel. K+ ions (C) and Tl+ (I) ions are sandwiched between G-quartets whereas Na+ (F) ions are located in plane with G-quartets. PDB entries (K+: IJPQ, Tl+: 2HBN and Na+: 1JB7).
Figure 5
Figure 5
Crystal structure of RNA G-quadruplex formed by the sequence (UGGGGU)4 in the presence of Sr2+ ions. The side view (A) and the view down the central ion channel (B) of the quadruplex. The schematic representation (C) shows that each Sr2+ ion is sandwiched by two G-quartets. (PDB entry 1J8G).
Figure 6
Figure 6
Structural switch in response to ionic environment in miRNA 92b may influence the processing and the biogenesis of the G-quadruplex harboring miRNAs.
See this image and copyright information in PMC

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