Sodium and Potassium Interactions with Nucleic Acids

Abstract

Metal ions are essential cofactors for the structure and functions of nucleic acids. Yet, the early discovery in the 70s of the crucial role of Mg(2+) in stabilizing tRNA structures has occulted for a long time the importance of monovalent cations. Renewed interest in these ions was brought in the late 90s by the discovery of specific potassium metal ions in the core of a group I intron. Their importance in nucleic acid folding and catalytic activity is now well established. However, detection of K(+) and Na(+) ions is notoriously problematic and the question about their specificity is recurrent. Here we review the different methods that can be used to detect K(+) and Na(+) ions in nucleic acid structures such as X-ray crystallography, nuclear magnetic resonance or molecular dynamics simulations. We also discuss specific versus non-specific binding to different structures through various examples.

Unraveling Mg2+–RNA binding with atomistic molecular dynamics

“…[16][17][18] However, the precise characterization of typical Mg 2+ binding sites in large RNA molecules has largely been obtained by analyzing crystal structures. 19,20 A recent database survey allowed for a classification of all the binding modes observed in crystallographic structures. 21 Molecular modeling could in principle provide a powerful tool to bridge the gap between detailed crystallographic structures and solution experiments.…”

Deflating the RNA Mg2+bubble. Stereochemistry to the rescue!

“…The latter ion, given its larger ionic radius, prefers binding modes with coordination numbers of 7 to 8, such as for example square anti-prismatic 1 (see UCSF Chimera 14 definition). These binding modes are recurrently observed in potassium channels, nucleic acid quadruplexes and other RNA systems 4,6,15 . K + and Mg 2+ have also distinct binding preferences 6,7 .…”

“…Given the much larger K + over Mg 2+ concentration in crystallo but also in vivo, it is not unreasonable to state that K + , along with polyamines 3,25,26 , is responsible for the largest part of the charge neutralization of ribosomes while Mg 2+ intervenes at a limited number of strategic locations to stabilize intricate structural folds 12 . This conclusion is not a surprise if we consider that Mg 2+ is a regulated resource in the cell that is used with parsimony and for specific structural purposes while K + is highly abundant [3][4][5] .…”

“…A recent publication by Rozov, Yusupova et al 1 (RY), emphasized that long-wavelength X-ray diffraction techniques can now be used to detect the presence of potassium ions (K + ) in large ribosome structures counting >150.000 heavy atoms. This accomplishment involved the use of the dedicated I23 in-vacuum long-wavelength beamline at the Diamond Light Source facility 2 to detect the anomalous signal of this biologically essential cation [3][4][5] . It allowed RY 1 to revisit the ribosome ionic structure proposing that electron density patterns, previously attributed to Mg 2+ , can now safely be associated with K + when coordination distances and geometries command it, as demonstrated earlier through the use of more candid stereochemically based methods 6,7 .…”

A new class of ribozyme from hepatitis B virus

“…So, what is the significance of the work? This element may represent an unusual new class of ribozyme with K + dependency . If so, it would be the second such ribozyme from hepatitis viruses, as hepatitis D virus (HDV) possesses a well‐studied ribozyme .…”