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Cited by 107RNA and protein synthesis mechanismsProtein Structure and DynamicsDNA and Nucleic Acid Chemistry

Magnesium-binding architectures in RNA crystal structures: validation, binding preferences, classification and motif detection

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Zheng, Heping, Shabalin, Ivan G., Handing, Katarzyna B., Bujnicki, Janusz M., Minor, Wladek·2015·Nucleic Acids Research
DOI 10.1093/nar/gkv225PMC PMC4402538
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Abstract

The ubiquitous presence of magnesium ions in RNA has long been recognized as a key factor governing RNA folding, and is crucial for many diverse functions of RNA molecules. In this work, Mg(2+)-binding architectures in RNA were systematically studied using a database of RNA crystal structures from the Protein Data Bank (PDB). Due to the abundance of poorly modeled or incorrectly identified Mg(2+) ions, the set of all sites was comprehensively validated and filtered to identify a benchmark dataset of 15 334 'reliable' RNA-bound Mg(2+) sites. The normalized frequencies by which specific RNA atoms coordinate Mg(2+) were derived for both the inner and outer coordination spheres. A hierarchical classification system of Mg(2+) sites in RNA structures was designed and applied to the benchmark dataset, yielding a set of 41 types of inner-sphere and 95 types of outer-sphere coordinating patterns. This classification system has also been applied to describe six previously reported Mg(2+)-binding motifs and detect them in new RNA structures. Investigation of the most populous site types resulted in the identification of seven novel Mg(2+)-binding motifs, and all RNA structures in the PDB were screened for the presence of these motifs.

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  • In the ribosome, just over half of ions assigned as Mg2+ retain four or more water molecules as ligands, with the most common RNA-associated inner sphere ligands being nonbridging oxygen atoms from the phosphate backbone.

    “In the ribosome, just over half of ions assigned as Mg2+ retain four or more water molecules as ligands, with the most common RNA-associated, inner sphere ligands being the nonbridging oxygen atoms from the phosphate backbone.65”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [65]

    The Results section on Mg2+ coordination reports that only around 30% of assigned ribosomal Mg2+ sites have even four or more inner-sphere ligands of any kind, contrary to the claim that just over half have four or more water ligands. The Results section on nucleotide-atom frequencies supports the other part: phosphate oxygen is the most commonly observed RNA inner-sphere ligand. Our copy provides no page numbers for these passages. (LLM, conf=0.90)

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  • The number of assigned Mg2+ ions varies widely, but in most cases Mg2+ is only sufficient to neutralize a fraction of the RNA charge, with the rest neutralized by ribosomal proteins and other cations.

    “The number of assigned Mg2+ ions varies widely, but in most cases Mg2+ is only sufficient to neutralize a fraction of the RNA charge,65 with the rest neutralized by ribosomal proteins and other cations.”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [65]

  • In ribosome structures from the PDB, over 20% of Mg2+ is fully hydrated with only outer-sphere coordination to the ribosome.

    “Similarly, in ribosome structures from the protein database (PDB) over 20% of Mg2+ is fully hydrated with only outer-sphere coordination to the ribosome.65”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [65]

  • A comprehensive analysis of >10^4 Mg2+ binding sites in RNA-containing structures reveals that ~1/3 of Mg2+ ions retain only water as inner sphere ligands.

    “A comprehensive analysis of >104 Mg2+ binding sites in RNA-containing structures reveals that ∼1/3 of Mg2+ ions retain only water as inner sphere ligands.65”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [65]

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Research works printed but not linked: 32

  1. [1]Draper D.E. RNA folding: Thermodynamic and molecular descriptions of the roles of ions Biophys. J. 2008 95 5489 5495 18835912 PMC2599833
  2. [2]Tinoco I. Jr Kieft J.S. The ion core in RNA folding Nat. Struct. Biol. 1997 4 509 512 9228937
  3. [3]Jenner L. Demeshkina N. Yusupova G. Yusupov M. Structural rearrangements of the ribosome at the tRNA proofreading step Nat. Struct. Mol. Biol. 2010 17 1072 1078 20694005
  4. [4]Brannvall M. Kirsebom L.A. Metal ion cooperativity in ribozyme cleavage of RNA Proc. Natl Acad. Sci. U.S.A. 2001 98 12943 12947 11606743 PMC60804
  5. [5]Scott W.G. Finch J.T. Klug A. The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage Cell 1995 81 991 1002 7541315
  6. [6]Bowman J.C. Lenz T.K. Hud N.V. Williams L.D. Cations in charge: magnesium ions in RNA folding and catalysis Curr. Opin. Struct. Biol. 2012 22 262 272 22595008
  7. [7]Ennifar E. Yusupov M. Walter P. Marquet R. Ehresmann B. Ehresmann C. Dumas P. The crystal structure of the dimerization initiation site of genomic HIV-1 RNA reveals an extended duplex with two adenine bulges Structure 1999 7 1439 1449 10574792
  8. [8]Correll C.C. Freeborn B. Moore P.B. Steitz T.A. Metals, motifs, and recognition in the crystal structure of a 5S rRNA domain Cell 1997 91 705 712 9393863
  9. [9]Baeyens K.J. De Bondt H.L. Pardi A. Holbrook S.R. A curved RNA helix incorporating an internal loop with G.A and A.A non-watson-crick base pairing Proc. Natl Acad. Sci. U.S.A. 1996 93 12851 12855 8917508 PMC24009
  10. [10]Klein D.J. Moore P.B. Steitz T.A. The contribution of metal ions to the structural stability of the large ribosomal subunit RNA 2004 10 1366 1379 15317974 PMC1370624
  11. [12]Hsiao C. Tannenbaum E. VanDeusen H. Hershkovitz E. Perng G. Tannenbaum A.R. Williams L.D. Hud NV Complexes of nucleic acids with group I and II cations Nucleic Acid-Metal Ion Interactions 2009 Cambridge RSC Publishing 1 38
  12. [13]Stefan L.R. Zhang R. Levitan A.G. Hendrix D.K. Brenner S.E. Holbrook S.R. MeRNA: a database of metal ion binding sites in RNA structures Nucleic Acids Res. 2006 34 D131 D134 16381830 PMC1347421
  13. [14]Schnabl J. Suter P. Sigel R.K. MINAS–a database of metal ions in nucleic AcidS Nucleic Acids Res. 2012 40 D434 D438 22096233 PMC3245035
  14. [15]Berman H.M. Westbrook J. Feng Z. Gilliland G. Bhat T.N. Weissig H. Shindyalov I.N. Bourne P.E. The protein data bank Nucleic Acids Res. 2000 28 235 242 10592235 PMC102472
  15. [16]Cooper D.R. Porebski P.J. Chruszcz M. Minor W. X-ray crystallography: assessment and validation of protein-small molecule complexes for drug discovery Expert Opin. Drug Discov. 2011 6 771 782 21779303 PMC3138648
  16. [17]Pozharski E. Weichenberger C.X. Rupp B. Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures Acta Crystallogr. D 2013 69 150 167 23385452
  17. [18]Zheng H. Chordia M.D. Cooper D.R. Chruszcz M. Muller P. Sheldrick G.M. Minor W. Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server Nat. Protoc. 2014 9 156 170 24356774 PMC4410975
  18. [19]Nayal M. Di Cera E. Valence screening of water in protein crystals reveals potential na+ binding sites J. Mol. Biol. 1996 256 228 234 8594192
  19. [20]Zheng H. Chruszcz M. Lasota P. Lebioda L. Minor W. Data mining of metal ion environments present in protein structures J. Inorg. Biochem. 2008 102 1765 1776 18614239 PMC2872550
  20. [21]Allen F.H. The Cambridge structural database: a quarter of a million crystal structures and rising Acta Cryst. B 2002 58 380 388 12037359
  21. [22]Permyakov E. Metalloproteomics 2009 Hoboken, NJ Wiley & Sons, Inc
  22. [23]Word J.M. Lovell S.C. LaBean T.H. Taylor H.C. Zalis M.E. Presley B.K. Richardson J.S. Richardson D.C. Visualizing and quantifying molecular goodness-of-fit: small-probe contact dots with explicit hydrogen atoms J. Mol. Biol. 1999 285 1711 1733 9917407
  23. [24]Chen V.B. Arendall W.B. III Headd J.J. Keedy D.A. Immormino R.M. Kapral G.J. Murray L.W. Richardson J.S. Richardson D.C. MolProbity: all-atom structure validation for macromolecular crystallography Acta Crystallogr. D 2010 66 12 21 20057044 PMC2803126
  24. [25]Winn M.D. Ballard C.C. Cowtan K.D. Dodson E.J. Emsley P. Evans P.R. Keegan R.M. Krissinel E.B. Leslie A.G. McCoy A. Overview of the CCP4 suite and current developments Acta Crystallogr. D Biol. Crystallogr. 2011 67 235 242 21460441 PMC3069738
  25. [27]Müller P. Köpke S. Sheldrick G.M. Is the bond-valence method able to identify metal atoms in protein structures Acta Cryst. D 2003 59 32 37 12499536
  26. [28]Borovinskaya M.A. Pai R.D. Zhang W. Schuwirth B.S. Holton J.M. Hirokawa G. Kaji H. Kaji A. Cate J.H. Structural basis for aminoglycoside inhibition of bacterial ribosome recycling Nat. Struct. Mol. Biol. 2007 14 727 732 17660832
  27. [29]Rabl J. Leibundgut M. Ataide S.F. Haag A. Ban N. Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1 Science 2011 331 730 736 21205638
  28. [30]Petrov A.S. Bowman J.C. Harvey S.C. Williams L.D. Bidentate RNA-magnesium clamps: on the origin of the special role of magnesium in RNA folding RNA 2011 17 291 297 21173199 PMC3022278
  29. [32]Hawkins P.C. Warren G.L. Skillman A.G. Nicholls A. How to do an evaluation: pitfalls and traps J. Comput. Aided Mol. Des. 2008 22 179 190 18217218 PMC2270916
  30. [33]Andreini C. Cavallaro G. Lorenzini S. Rosato A. MetalPDB: a database of metal sites in biological macromolecular structures Nucleic Acids Res. 2013 41 D312 D319 23155064 PMC3531106
  31. [34]Castagnetto J.M. Hennessy S.W. Roberts V.A. Getzoff E.D. Tainer J.A. Pique M.E. MDB: the metalloprotein database and browser at the scripps research institute Nucleic Acids Res. 2002 30 379 382 11752342 PMC99158
  32. [36]Philips A. Milanowska K. Lach G. Boniecki M. Rother K. Bujnicki J.M. MetalionRNA: computational predictor of metal-binding sites in RNA structures Bioinformatics 2012 28 198 205 22110243 PMC3259437

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Authors
Zheng, H., Shabalin, I. G., Handing, K. B., Bujnicki, J. M., & Minor, W.
Affiliations
  • University of Virginia (US)
  • International Institute of Molecular and Cell Biology (PL)
Corresponding author
Minor, Wladek
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2015-03-23
Volume
43
Issue
7
Pages
3789-3801
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkv225
PMC
PMC4402538
OpenAlex
W2035334116
Cited by
107
References
0
Citations by year
2026: 7 · 2025: 9 · 2024: 13 · 2023: 8 · 2022: 11 · 2021: 7 · 2020: 10 · 2019: 7 · 2018: 14 · 2017: 11 · 2016: 7 · 2015: 2
FWCI
4.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services (HHSN272201200026C)
  • Fundacja na rzecz Nauki Polskiej (TEAM/2009–4/2)
  • National Institutes of Health (HHSN272201200026C, GM094585, GM093342, GM094662)
  • U.S. Public Health Service (HHSN272201200026C)
  • National Institute of General Medical Sciences (U54GM093342, U54GM094662, GM094662, U54GM094585, GM093342, GM094585)
  • National Institute of Allergy and Infectious Diseases (GM094585, HHSN272201200026C)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
magnesium ions, RNA, Mg2+ binding site, RNA crystal structure, coordination sphere, binding site classification, binding motifs, RNA folding, motif discovery
MeSH terms
Binding Sites, Magnesium, Nucleic Acid Conformation, RNA, Crystallography, X-Ray

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