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Understanding the Thermodynamics of Magnesium Binding to RNA Structural Motifs

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Cowan, J. A.·2024·Life
DOI 10.3390/life14060765PMC PMC11205036
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Abstract

Divalent magnesium ions (Mg2+) serve a vital role in defining the structural and catalytic chemistry of a wide array of RNA molecules. The body of structural information on RNA motifs continues to expand and, in turn, the functional importance of Mg2+ is revealed. A combination of prior work on the structural characterization of magnesium binding ligands with inner- and outer-sphere coordination modes, with recorded experimental binding energies for inner- and outer-sphere contacts, demonstrates the relative affinity and thermodynamic hierarchy for these sites. In turn, these can be correlated with cellular concentrations of free available magnesium ions, allowing the prioritization of populating important functional sites and a correlation with physiological function. This paper summarizes some of the key results of that analysis and provides predictive rules for the affinity and role of newly identified Mg binding sites on complex RNA structures. The influence of crystal packing on magnesium binding to RNA motifs, relative to their solution form, is addressed and caveats made.

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  • Both Mg2+ and K+ function in charge neutralization as mobile, outer-sphere ions, with Mg2+ favored at sites of unusually high negative charge density.

    “Both Mg2+ and K+ therefore function in charge neutralization as mobile, outer-sphere ions, with Mg2+ favored at sites of unusually high negative charge density.66”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [66]

    The Discussion (§§4.1–4.2) describes outer-sphere Mg2+ binding in charge neutralization, and the Conclusions (§4.7) say K+ can neutralize charge while Mg2+ is used at unusually negative pockets. The cited passages do not establish that K+ acts specifically as a mobile, outer-sphere ion. (LLM, conf=0.82)

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Research works printed but not linked: 25

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Authors
Cowan, J. A.
Affiliations
The Ohio State University (US)
Corresponding author
Cowan, J. A.
ORCID
Cowan, J. A.
Venue
Life
Publisher
MDPI AG
Published
2024-06-16
Volume
14
Issue
6
Pages
765
ISSN
2075-1729 (ISSN-L)
DOI
10.3390/life14060765
PMC
PMC11205036
OpenAlex
W4399759004
Cited by
5
References
0
Citations by year
2026: 3 · 2025: 2
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Life (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
magnesium binding, RNA structural motifs, divalent cations, inner-sphere coordination, outer-sphere coordination, binding thermodynamics, binding affinity, crystal packing effects, RNA structure-function, magnesium content

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