Ion Condensation onto Ribozyme Is Site Specific and Fold Dependent

Hori, Naoto; Denesyuk, Natalia A.; Thirumalai, D.

Abstract

The highly charged RNA molecules, with each phosphate carrying a single negative charge, cannot fold into well-defined architectures with tertiary interactions in the absence of ions. For ribozymes, divalent cations are known to be more efficient than monovalent ions in driving them to a compact state, although Mg2+ ions are needed for catalytic activities. Therefore, how ions interact with RNA is relevant in understanding RNA folding. It is often thought that most of the ions are territorially and nonspecifically bound to the RNA, as predicted by the counterion condensation theory. Here, we show using simulations of Azoarcus ribozyme, based on an accurate coarse-grained three-site interaction model with explicit divalent and monovalent cations, that ion condensation is highly specific and depends on the nucleotide position. The regions with high coordination between the phosphate groups and the divalent cations are discernible even at very low Mg2+ concentrations when the ribozyme does not form tertiary interactions. Surprisingly, these regions also contain the secondary structural elements that nucleate subsequently in the self-assembly of RNA, implying that ion condensation is determined by the architecture of the folded state. These results are in sharp contrast to interactions of ions (monovalent and divalent) with rigid charged rods, in which ion condensation is uniform and position independent. The differences are explained in terms of the dramatic nonmonotonic shape fluctuations in the ribozyme as it folds with increasing Mg2+ or Ca2+ concentration.

• Journal Article Type: Article
• Acceptance Date: Apr 23, 2019
• Online Publication Date: May 11, 2019
• Publication Date: 2019-06
• Deposit Date: Sep 19, 2020
• Journal: Biophysical Journal
• Print ISSN: 0006-3495
• Electronic ISSN: 1542-0086
• Publisher: Biophysical Society
• Peer Reviewed: Peer Reviewed
• Volume: 116
• Issue: 12
• Pages: 2400-2410
• DOI: https://doi.org/10.1016/j.bpj.2019.04.037
• Keywords: Biophysics
• Public URL: https://nottingham-repository.worktribe.com/output/4342472
• Publisher URL: https://www.cell.com/biophysj/fulltext/S0006-3495(19)30388-1
• Related Public URLs: https://www.sciencedirect.com/science/article/pii/S0006349519303881
• Additional Information: This article is maintained by: Elsevier; Article Title: Ion Condensation onto Ribozyme Is Site Specific and Fold Dependent; Journal Title: Biophysical Journal; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.bpj.2019.04.037; CrossRef DOI link to the associated document: https://doi.org/10.1016/j.bpj.2019.04.038; Content Type: article; Copyright: © 2019 Biophysical Society.