A thermodynamic framework for Mg2+ binding to RNA

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FONTE

The National Academy of Sciences

RESUMO

We present a model describing how Mg2+ binds and stabilizes specific RNA structures. In this model, RNA stabilization arises from two energetically distinct modes of Mg2+ binding: diffuse- and site-binding. Diffusely bound Mg2+ are electrostatically attracted to the strong anionic field around the RNA and are accurately described by the Poisson–Boltzmann equation as an ensemble distributed according to the electrostatic potentials around the nucleic acid. Site-bound Mg2+ are strongly attracted to specifically arranged electronegative ligands that desolvate the ion and the RNA binding site. Thus, site-binding is a competition between the strong coulombic attraction and the large cost of desolvating the ion and its binding pocket. By using this framework, we analyze three systems where a single site-bound Mg2+ may be important for stability: the P5 helix and the P5b stem loop from the P4-P6 domain of the Tetrahymena thermophila group I intron and a 58-nt fragment of the Escherichia coli 23S ribosomal RNA. Diffusely bound Mg2+ play a dominant role in stabilizing these RNA structures. These ions stabilize the folded structures, in part, by accumulating in regions of high negative electrostatic potential. These regions of Mg2+ localization correspond to ions that are observed in the x-ray crystallographic and NMR structures of the RNA. In contrast, the contribution of site-binding to RNA stability is often quite small because of the large desolvation penalty. However, in special cases, site-binding of partially dehydrated Mg2+ to locations with extraordinarily high electrostatic potential can also help stabilize folded RNA structures.

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