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Metal Cations in G-Quadruplex Folding and Stability

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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.

No MeSH data available.


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).
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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).

Mentions: Telomric G-rich sequences form various species are the most well characterized among GQs formed by naturally occurring sequences. Crystallographic study suggests that Oxytricha nova telomere sequence d(G4T4G4) forms a bimolecular quadruplex with four quartets. A linear row of five equidistant K+ ions lie along the central axis with an average distance of 3.38 Å between any two K+ ions in tandem (Figures 4A–C). The K+ ions are ad libitum equidistant from the planes of two adjacent G-quartets. Moreover, the outer K+ ions are located outside the GQ structure where they coordinate with the terminal quartets and O2 atoms of the loop residues, and water molecules (Haider et al., 2002). The same sequence in presence of Tl+, which is a perfect surrogate of K+ forms a structure which is very similar to the structure formed in presence of K+ (Figures 4G–I). Furthermore, the coordination of the Tl+ ions is similar to the K+ ions as described above (Gill et al., 2006). However, in presence of Na+ ions the structure indicates that the central Na+ ions are nearly coplanar with the G-quartets (Figures 4D–F). The outer Na+ ions are positioned beyond the planes of the flanking quartets more toward the loops where they coordinate with the quartet O6 and O2 atoms of the thymine bases in the loops (Horvath and Schultz, 2001; Haider et al., 2002).


Metal Cations in G-Quadruplex Folding and Stability
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).
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Related In: Results  -  Collection

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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).
Mentions: Telomric G-rich sequences form various species are the most well characterized among GQs formed by naturally occurring sequences. Crystallographic study suggests that Oxytricha nova telomere sequence d(G4T4G4) forms a bimolecular quadruplex with four quartets. A linear row of five equidistant K+ ions lie along the central axis with an average distance of 3.38 Å between any two K+ ions in tandem (Figures 4A–C). The K+ ions are ad libitum equidistant from the planes of two adjacent G-quartets. Moreover, the outer K+ ions are located outside the GQ structure where they coordinate with the terminal quartets and O2 atoms of the loop residues, and water molecules (Haider et al., 2002). The same sequence in presence of Tl+, which is a perfect surrogate of K+ forms a structure which is very similar to the structure formed in presence of K+ (Figures 4G–I). Furthermore, the coordination of the Tl+ ions is similar to the K+ ions as described above (Gill et al., 2006). However, in presence of Na+ ions the structure indicates that the central Na+ ions are nearly coplanar with the G-quartets (Figures 4D–F). The outer Na+ ions are positioned beyond the planes of the flanking quartets more toward the loops where they coordinate with the quartet O6 and O2 atoms of the thymine bases in the loops (Horvath and Schultz, 2001; Haider et al., 2002).

View Article: PubMed Central - PubMed

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.

No MeSH data available.