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Diffusion NMR-based comparison of electrostatic influences of DNA on various monovalent cations

      Abstract

      Counterions are important constituents for the structure and function of nucleic acids. Using 7Li and 133Cs nuclear magnetic resonance (NMR) spectroscopy, we investigated how ionic radii affect the behavior of counterions around DNA through diffusion measurements of Li+ and Cs+ ions around a 15-bp DNA duplex. Together with our previous data on 23Na+ and 15NH4+ ions around the same DNA under the same conditions, we were able to compare the dynamics of four different monovalent ions around DNA. From the apparent diffusion coefficients at varied concentrations of DNA, we determined the diffusion coefficients of these cations inside and outside the ion atmosphere around DNA (Db and Df, respectively). We also analyzed ionic competition with K+ ions for the ion atmosphere and assessed the relative affinities of these cations for DNA. Interestingly, all cations (i.e., Li+, Na+, NH4+, and Cs+) analyzed by diffusion NMR spectroscopy exhibited nearly identical Db/Df ratios despite the differences in their ionic radii, relative affinities, and diffusion coefficients. These results, along with the theoretical relationship between diffusion and entropy, suggest that the entropy change due to the release of counterions from the ion atmosphere around DNA is also similar regardless of the monovalent ion types. These findings and the experimental diffusion data on the monovalent ions are useful for examination of computational models for electrostatic interactions or ion solvation.
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      References

        • Jacobson D.R.
        • Saleh O.A.
        Counting the ions surrounding nucleic acids.
        Nucleic Acids Res. 2017; 45: 1596-1605https://doi.org/10.1093/nar/gkw1305
        • Schurr J.M.
        Polyanion models of nucleic acid–metal ion interactions.
        in: Hud N.V. Nucleic Acid-Metal Ion Interactions. RSC Publishing, 2008: 307-349
        • Lipfert J.
        • Doniach S.
        • Herschlag D.
        • et al.
        Understanding nucleic acid-ion interactions.
        Annu. Rev. Biochem. 2014; 83: 813-841https://doi.org/10.1146/annurev-biochem-060409-092720
        • Yu B.
        • Iwahara J.
        Experimental approaches for investigating ion atmospheres around nucleic acids and proteins.
        Comput. Struct. Biotechnol. J. 2021; 19: 2279-2285https://doi.org/10.1016/j.csbj.2021.04.033
        • Manning G.S.
        Counterion binding in polyelectrolyte theory.
        Acc. Chem. Res. 1979; 12: 443-449https://doi.org/10.1021/ar50144a004
        • Bai Y.
        • Greenfeld M.
        • Herschlag D.
        • et al.
        Quantitative and comprehensive decomposition of the ion atmosphere around nucleic acids.
        J. Am. Chem. Soc. 2007; 129: 14981-14988https://doi.org/10.1021/ja075020g
        • Bai Y.
        • Das R.
        • Doniach S.
        • et al.
        Probing counterion modulated repulsion and attraction between nucleic acid duplexes in solution.
        Proc. Natl. Acad. Sci. USA. 2005; 102: 1035-1040https://doi.org/10.1073/pnas.0404448102
        • Privalov P.L.
        • Dragan A.I.
        • Crane-Robinson C.
        Interpreting protein/DNA interactions: distinguishing specific from non-specific and electrostatic from non-electrostatic components.
        Nucleic Acids Res. 2011; 39: 2483-2491https://doi.org/10.1093/nar/gkq984
        • Record M.T.
        • Anderson C.F.
        • Lohman T.M.
        Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: the roles of ion association or release, screening, and ion effects on water activity.
        Q. Rev. Biophys. 1978; 11: 103-178https://doi.org/10.1017/s003358350000202x
        • Bleam M.L.
        • Anderson C.F.
        • Record M.T.
        Relative binding affinities of monovalent cations for double-stranded DNA.
        Proc. Natl. Acad. Sci. USA. 1980; 77: 3085-3089https://doi.org/10.1073/pnas.77.6.3085
        • Hud N.V.
        • Feigon J.
        Characterization of divalent cation localization in the minor groove of the AnTn and TnAn DNA sequence elements by 1H NMR spectroscopy and manganese(II).
        Biochemistry. 2002; 41: 9900-9910https://doi.org/10.1021/bi020159j
        • Hud N.V.
        • Feigon J.
        Localization of divalent metal ions in the minor groove of DNA A-tracts.
        J. Am. Chem. Soc. 1997; 119: 5756-5757https://doi.org/10.1021/ja9704085
        • Hud N.V.
        • Sklenar V.
        • Feigon J.
        Localization of ammonium ions in the minor groove of DNA duplexes in solution and the origin of DNA A-tract bending.
        J. Mol. Biol. 1999; 286: 651-660https://doi.org/10.1006/jmbi.1998.2513
        • Denisov V.P.
        • Halle B.
        Sequence-specific binding of counterions to B-DNA.
        Proc. Natl. Acad. Sci. USA. 2000; 97: 629-633https://doi.org/10.1073/pnas.97.2.629
        • Cesare Marincola F.
        • Denisov V.P.
        • Halle B.
        Competitive Na+ and Rb+ binding in the minor groove of DNA.
        J. Am. Chem. Soc. 2004; 126: 6739-6750https://doi.org/10.1021/ja049930z
        • Pletka C.C.
        • Nepravishta R.
        • Iwahara J.
        Detecting counterion dynamics in DNA-protein association.
        Angew Chem. Int. Ed. Engl. 2020; 132: 1481-1484https://doi.org/10.1002/ange.201910960
        • Yu B.
        • Bien K.G.
        • Iwahara J.
        • et al.
        Dynamics of cations around DNA and protein as revealed by 23Na diffusion NMR spectroscopy.
        Anal. Chem. 2022; 94: 2444-2452https://doi.org/10.1021/acs.analchem.1c04197
        • Gebala M.
        • Giambaşu G.M.
        • Herschlag D.
        • et al.
        Cation-anion interactions within the nucleic acid ion atmosphere revealed by ion counting.
        J. Am. Chem. Soc. 2015; 137: 14705-14715https://doi.org/10.1021/jacs.5b08395
        • Gebala M.
        • Bonilla S.
        • Herschlag D.
        • et al.
        Does cation size affect occupancy and electrostatic screening of the nucleic acid ion atmosphere?.
        J. Am. Chem. Soc. 2016; 138: 10925-10934https://doi.org/10.1021/jacs.6b04289
        • Anderson B.J.
        • Larkin C.
        • Schildbach J.F.
        • et al.
        Using fluorophore-labeled oligonucleotides to measure affinities of protein-DNA interactions.
        Methods Enzymol. 2008; 450: 253-272https://doi.org/10.1016/S0076-6879(08)03412-5
        • Pabit S.A.
        • Meisburger S.P.
        • Pollack L.
        • et al.
        Counting ions around DNA with anomalous small-angle X-ray scattering.
        J. Am. Chem. Soc. 2010; 132: 16334-16336https://doi.org/10.1021/ja107259y
        • Meisburger S.P.
        • Pabit S.
        • Pollack L.
        • et al.
        Determining the locations of ions and water around DNA from X-ray scattering measurements.
        Biophys. J. 2015; 108: 2886-2895https://doi.org/10.1016/j.bpj.2015.05.006
        • Cheng Y.
        • Korolev N.
        • Nordenskiöld L.
        Similarities and differences in interaction of K+ and Na+ with condensed ordered DNA. A molecular dynamics computer simulation study.
        Nucleic Acids Res. 2006; 34: 686-696https://doi.org/10.1093/nar/gkj434
        • Giambaşu G.M.
        • Gebala M.K.
        • York D.M.
        • et al.
        Competitive interaction of monovalent cations with DNA from 3D-RISM.
        Nucleic Acids Res. 2015; 43: 8405-8415https://doi.org/10.1093/nar/gkv830
        • Howard J.J.
        • Lynch G.C.
        • Pettitt B.M.
        Ion and solvent density distributions around canonical B-DNA from integral equations.
        J. Phys. Chem. B. 2011; 115: 547-556https://doi.org/10.1021/jp107383s
        • Kolesnikov E.S.
        • Gushchin I.Y.
        • Onufriev A.V.
        • et al.
        Similarities and differences between Na+ and K+ distributions around DNA obtained with three popular water models.
        J. Chem. Theor. Comput. 2021; 17: 7246-7259https://doi.org/10.1021/acs.jctc.1c00332
        • Savelyev A.
        • MacKerell Jr., A.D.
        Competition among Li+, Na+, K+, and Rb+ monovalent ions for DNA in molecular dynamics simulations using the additive CHARMM36 and Drude polarizable force fields.
        J. Phys. Chem. B. 2015; 119: 4428-4440https://doi.org/10.1021/acs.jpcb.5b00683
        • Savelyev A.
        • Papoian G.A.
        Electrostatic, steric, and hydration interactions favor Na+ condensation around DNA compared with K+.
        J. Am. Chem. Soc. 2006; 128: 14506-14518https://doi.org/10.1021/ja0629460
        • Yu B.
        • Pettitt B.M.
        • Iwahara J.
        Dynamics of ionic interactions at protein–nucleic acid interfaces.
        Acc. Chem. Res. 2020; 53: 1802-1810https://doi.org/10.1021/acs.accounts.0c00212
        • Seki K.
        • Bagchi B.
        Relationship between entropy and diffusion: a statistical mechanical derivation of Rosenfeld expression for a rugged energy landscape.
        J. Chem. Phys. 2015; 143: 194110https://doi.org/10.1063/1.4935969
        • Marcus Y.
        Ionic radii in aqueous solutions.
        Chem. Rev. 1988; 88: 1475-1498https://doi.org/10.1021/cr00090a003
        • Hayamizu K.
        • Price W.S.
        A new type of sample tube for reducing convection effects in PGSE-NMR measurements of self-diffusion coefficients of liquid samples.
        J. Magn. Reson. 2004; 167: 328-333https://doi.org/10.1016/j.jmr.2004.01.006
        • Harris R.K.
        • Becker E.D.
        • Granger P.
        • et al.
        NMR nomenclature. Nuclear spin properties and conventions for chemical shifts(IUPAC Recommendations 2001).
        Pure Appl. Chem. 2001; 73: 1795-1818https://doi.org/10.1351/pac200173111795
        • Wu D.H.
        • Chen A.D.
        • Johnson C.S.
        An improved diffusion-ordered spectroscopy experiment incorporating bipolar-gradient pulses.
        J. Magn. Reson. Ser. A. 1995; 115: 260-264https://doi.org/10.1006/jmra.1995.1176
        • Johnson C.S.
        Diffusion ordered nuclear magnetic resonance spectroscopy: principles and applications.
        Prog. NMR Spect. 1999; 34: 203-256https://doi.org/10.1016/s0079-6565(99)00003-5
        • Holz M.
        • Weingartner H.
        Calibration in accurate spin-echo self-diffusion measurements using 1H and less-common nuclei.
        J. Magn. Reson. 1991; 92: 115-125https://doi.org/10.1016/0022-2364(91)90252-o
        • Johnson C.S.
        Effects of chemical exchange in diffusion-ordered 2D NMR spectra.
        J. Magn. Reson. Ser. A. 1993; 102: 214-218https://doi.org/10.1006/jmra.1993.1093
        • Gebala M.
        • Herschlag D.
        Quantitative studies of an RNA duplex electrostatics by ion counting.
        Biophys. J. 2019; 117: 1116-1124https://doi.org/10.1016/j.bpj.2019.08.007
        • Vanýsek P.
        Ionic conductivity and diffusion at infinite dilution.
        in: Lide D.R. CRC Handbook of Chemistry and Physics. 84th edition. CRC Press, 2003: 595-597
        • Sidey V.
        On the effective ionic radii for ammonium.
        Acta Crystallogr. B. 2016; 72: 626-633https://doi.org/10.1107/s2052520616008064
        • Collins K.D.
        Charge density-dependent strength of hydration and biological structure.
        Biophys. J. 1997; 72: 65-76https://doi.org/10.1016/s0006-3495(97)78647-8
        • Marcus Y.
        Electrostriction, ion solvation, and solvent release on ion pairing.
        J. Phys. Chem. B. 2005; 109: 18541-18549https://doi.org/10.1021/jp051505k
        • Giambaşu G.M.
        • Case D.A.
        • York D.M.
        Predicting site-binding modes of ions and water to nucleic acids using molecular solvation theory.
        J. Am. Chem. Soc. 2019; 141: 2435-2445https://doi.org/10.1021/jacs.8b11474
        • Shui X.
        • McFail-Isom L.
        • Williams L.D.
        • et al.
        The B-DNA dodecamer at high resolution reveals a spine of water on sodium.
        Biochemistry. 1998; 37: 8341-8355https://doi.org/10.1021/bi973073c
        • Tereshko V.
        • Wilds C.J.
        • Egli M.
        • et al.
        Detection of alkali metal ions in DNA crystals using state-of-the-art X-ray diffraction experiments.
        Nucleic Acids Res. 2001; 29: 1208-1215https://doi.org/10.1093/nar/29.5.1208
        • Pasi M.
        • Maddocks J.H.
        • Lavery R.
        Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics.
        Nucleic Acids Res. 2015; 43: 2412-2423https://doi.org/10.1093/nar/gkv080
        • Varnai P.
        • Zakrzewska K.
        DNA and its counterions: a molecular dynamics study.
        Nucleic Acids Res. 2004; 32: 4269-4280https://doi.org/10.1093/nar/gkh765
        • Auffinger P.
        • Westhof E.
        Water and ion binding around RNA and DNA (C, G) oligomers.
        J. Mol. Biol. 2000; 300: 1113-1131https://doi.org/10.1006/jmbi.2000.3894
        • He W.
        • Chen Y.-L.
        • Kirmizialtin S.
        • et al.
        The structural plasticity of nucleic acid duplexes revealed by WAXS and MD.
        Sci. Adv. 2021; 7: eabf6106https://doi.org/10.1126/sciadv.abf6106
        • Zwanzig R.
        Diffusion in a rough potential.
        Proc. Natl. Acad. Sci. USA. 1988; 85: 2029-2030https://doi.org/10.1073/pnas.85.7.2029
        • Ha J.H.
        • Capp M.W.
        • Record M.
        • et al.
        Thermodynamic stoichiometries of participation of water, cations and anions in specific and non-specific binding of lac repressor to DNA.
        J. Mol. Biol. 1992; 228: 252-264https://doi.org/10.1016/0022-2836(92)90504-d
        • Maslak M.
        • Martin C.T.
        Effects of solution conditions on the steady-state kinetics of initiation of transcription by T7 RNA polymerase.
        Biochemistry. 1994; 33: 6918-6924https://doi.org/10.1021/bi00188a022
        • Overman L.B.
        • Bujalowski W.
        • Lohman T.M.
        Equilibrium binding of Escherichia coli single-strand binding protein to single-stranded nucleic acids in the (SSB)65 binding mode. Cation and anion effects and polynucleotide specificity.
        Biochemistry. 1988; 27: 456-471https://doi.org/10.1021/bi00401a067
        • Yu B.
        • Pletka C.C.
        • Iwahara J.
        Quantifying and visualizing weak interactions between anions and proteins.
        Proc. Natl. Acad. Sci. USA. 2021; 118 (e2015879118)https://doi.org/10.1073/pnas.2015879118
        • Joung I.S.
        • Cheatham T.E.
        Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations.
        J. Phys. Chem. B. 2008; 112: 9020-9041https://doi.org/10.1021/jp8001614
        • Yu B.
        • Pletka C.C.
        • Iwahara J.
        Protein electrostatics investigated through paramagnetic NMR for nonpolar groups.
        J. Phys. Chem. B. 2022; 126: 2196-2202https://doi.org/10.1021/acs.jpcb.1c10930
        • Yu B.
        • Pletka C.C.
        • Pettitt B.M.
        • Iwahara J.
        De novo determination of near-surface electrostatic potentials by NMR.
        Proc. Natl. Acad. Sci. USA. 2021; 118 (e2104020118)https://doi.org/10.1073/pnas.2104020118
        • Chen C.
        • Yu B.
        • Yousefi R.
        • Iwahara J.
        • Pettitt B.M.
        Assessment of the components of the electrostatic potential of proteins in solution: comparing experiment and theory.
        J. Phys. Chem. B. 2022; 126: 4543-4554https://doi.org/10.1021/acs.jpcb.2c01611