A thermodynamic framework for Mg2+ binding to RNA

Vinod K. Misra, David E. Draper

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)12456-12461
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number22
DOIs
StatePublished - Oct 23 2001

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