Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Nov;77(5):2736–2749. doi: 10.1016/s0006-3495(99)77107-9

Competitive binding of mg(2+), ca(2+), na(+), and K(+) ions to DNA in oriented DNA fibers: experimental and monte carlo simulation results

N Korolev 1, AP Lyubartsev 1, A Rupprecht 1, L Nordenskiold 1
PMCID: PMC1300547  PMID: 10545373

Abstract

Competitive binding of the most common cations of the cytoplasm (K(+), Na(+), Ca(2+), and Mg(2+)) with DNA was studied by equilibrating oriented DNA fibers with ethanol/water solutions (65 and 52% v/v EtOH) containing different combinations and concentrations of the counterions. The affinity of DNA for the cations decreases in the order Ca > Mg >> Na approximately K. The degree of Ca(2+) and/or Mg(2+) binding to DNA displays maximum changes just at physiological concentrations of salts (60-200 mM) and does not depend significantly on the ethanol concentration or on the kind of univalent cation (Na(+) or K(+)). Ca(2+) is more tightly bound to DNA and is replaced by the monovalent cations to a lesser extent than is Mg(2+). Similarly, Ca(2+) is a better competitor for binding to DNA than Mg(2+): the ion exchange equilibrium constant for a 1:1 mixture of Ca(2+) and Mg(2+) ions, K(c)(Ca)(Mg), changes from K(c)(Ca)(Mg) approximately 2 in 65% EtOH (in 3-30 mM NaCl and/or KCl) to K(c)(Ca)(Mg) approximately 1.2-1.4 in 52% EtOH (in 300 mM NaCl and/or KCl). DNA does not exhibit selectivity for Na(+) or K(+) in ethanol/water solutions either in the absence or in the presence of Ca(2+) and/or Mg(2+). The ion exchange experimental data are compared with results of grand canonical Monte Carlo (GCMC) simulations of systems of parallel and hexagonally ordered, uniformly and discretely charged polyions with the density and spatial distribution of the charged groups modeling B DNA. A quantitative agreement with experimental data on divalent-monovalent competition has been obtained for discretely charged models of the DNA polyion (for the uniformly charged cylinder model, coincidence with experiment is qualitative). The GCMC method gives also a qualitative description of experimental results for DNA binding competitions of counterions of the same charge (Ca(2+) with Mg(2+) or K(+) with Na(+)).

Full Text

The Full Text of this article is available as a PDF (191.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bleam M. L., Anderson C. F., Record M. T. Relative binding affinities of monovalent cations for double-stranded DNA. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3085–3089. doi: 10.1073/pnas.77.6.3085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braunlin W. H., Anderson C. F., Record M. T. 23Na-NMR investigations of counterion exchange reactions of helical DNA. Biopolymers. 1986 Jan;25(1):205–214. doi: 10.1002/bip.360250114. [DOI] [PubMed] [Google Scholar]
  3. Braunlin W. H., Drakenberg T., Nordenskiöld L. A 43Ca-NMR study of Ca(II)-DNA interactions. Biopolymers. 1987 Jul;26(7):1047–1062. doi: 10.1002/bip.360260705. [DOI] [PubMed] [Google Scholar]
  4. Braunlin W. H., Drakenberg T., Nordenskiöld L. Ca2+ binding environments on natural and synthetic polymeric DNA's. J Biomol Struct Dyn. 1992 Oct;10(2):333–343. doi: 10.1080/07391102.1992.10508651. [DOI] [PubMed] [Google Scholar]
  5. Braunlin W. H., Nordenskiöld L., Drakenberg T. A reexamination of 25Mg2+ NMR in DNA solution: site heterogeneity and cation competition effects. Biopolymers. 1991 Oct;31(11):1343–1346. doi: 10.1002/bip.360311111. [DOI] [PubMed] [Google Scholar]
  6. Braunlin W. H., Nordenskiöld L., Drakenberg T. The interaction of calcium (II) with DNA probed by 43Ca-NMR is not influenced by terminal phosphate groups at ends and nicks. Biopolymers. 1989 Jul;28(7):1339–1342. doi: 10.1002/bip.360280713. [DOI] [PubMed] [Google Scholar]
  7. Butler J. N. The thermodynamic activity of calcium ion in sodium chloride-calcium chloride electrolytes. Biophys J. 1968 Dec;8(12):1426–1433. doi: 10.1016/S0006-3495(68)86564-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collins K. D. Charge density-dependent strength of hydration and biological structure. Biophys J. 1997 Jan;72(1):65–76. doi: 10.1016/S0006-3495(97)78647-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dawson W. D., Smith T. C. Intracellular Na+, K+ and Cl- activities in Ehrlich ascites tumor cells. Biochim Biophys Acta. 1986 Aug 21;860(2):293–300. doi: 10.1016/0005-2736(86)90526-2. [DOI] [PubMed] [Google Scholar]
  10. Dobi A., v Agoston D. Submillimolar levels of calcium regulates DNA structure at the dinucleotide repeat (TG/AC)n. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5981–5986. doi: 10.1073/pnas.95.11.5981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Doyle D. A., Morais Cabral J., Pfuetzner R. A., Kuo A., Gulbis J. M., Cohen S. L., Chait B. T., MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998 Apr 3;280(5360):69–77. doi: 10.1126/science.280.5360.69. [DOI] [PubMed] [Google Scholar]
  12. Gilli R., Lafitte D., Lopez C., Kilhoffer M., Makarov A., Briand C., Haiech J. Thermodynamic analysis of calcium and magnesium binding to calmodulin. Biochemistry. 1998 Apr 21;37(16):5450–5456. doi: 10.1021/bi972083a. [DOI] [PubMed] [Google Scholar]
  13. Ha J. H., Capp M. W., Hohenwalter M. D., Baskerville M., Record M. T., Jr Thermodynamic stoichiometries of participation of water, cations and anions in specific and non-specific binding of lac repressor to DNA. Possible thermodynamic origins of the "glutamate effect" on protein-DNA interactions. J Mol Biol. 1992 Nov 5;228(1):252–264. doi: 10.1016/0022-2836(92)90504-d. [DOI] [PubMed] [Google Scholar]
  14. Jayaram B., Beyeridge D. L. Modeling DNA in aqueous solutions: theoretical and computer simulation studies on the ion atmosphere of DNA. Annu Rev Biophys Biomol Struct. 1996;25:367–394. doi: 10.1146/annurev.bb.25.060196.002055. [DOI] [PubMed] [Google Scholar]
  15. Ling G. N. The new cell physiology: an outline, presented against its full historical background, beginning from the beginning. Physiol Chem Phys Med NMR. 1994;26(2):121–203. [PubMed] [Google Scholar]
  16. Lyubartsev A. P., Laaksonen A. Molecular dynamics simulations of DNA in solutions with different counter-ions. J Biomol Struct Dyn. 1998 Dec;16(3):579–592. doi: 10.1080/07391102.1998.10508271. [DOI] [PubMed] [Google Scholar]
  17. Mirzabekov A. D., Rich A. Asymmetric lateral distribution of unshielded phosphate groups in nucleosomal DNA and its role in DNA bending. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1118–1121. doi: 10.1073/pnas.76.3.1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nguyen T., Chin W. C., Verdugo P. Role of Ca2+/K+ ion exchange in intracellular storage and release of Ca2+. Nature. 1998 Oct 29;395(6705):908–912. doi: 10.1038/27686. [DOI] [PubMed] [Google Scholar]
  19. Paulsen M. D., Anderson C. F., Record M. T., Jr Counterion exchange reactions on DNA: Monte Carlo and Poisson-Boltzmann analysis. Biopolymers. 1988 Aug;27(8):1249–1265. doi: 10.1002/bip.360270806. [DOI] [PubMed] [Google Scholar]
  20. Record M. T., Jr, Courtenay E. S., Cayley D. S., Guttman H. J. Responses of E. coli to osmotic stress: large changes in amounts of cytoplasmic solutes and water. Trends Biochem Sci. 1998 Apr;23(4):143–148. doi: 10.1016/s0968-0004(98)01196-7. [DOI] [PubMed] [Google Scholar]
  21. Record M. T., Jr, Courtenay E. S., Cayley S., Guttman H. J. Biophysical compensation mechanisms buffering E. coli protein-nucleic acid interactions against changing environments. Trends Biochem Sci. 1998 May;23(5):190–194. doi: 10.1016/s0968-0004(98)01207-9. [DOI] [PubMed] [Google Scholar]
  22. Record M. T., Jr, Zhang W., Anderson C. F. Analysis of effects of salts and uncharged solutes on protein and nucleic acid equilibria and processes: a practical guide to recognizing and interpreting polyelectrolyte effects, Hofmeister effects, and osmotic effects of salts. Adv Protein Chem. 1998;51:281–353. doi: 10.1016/s0065-3233(08)60655-5. [DOI] [PubMed] [Google Scholar]
  23. Rose D. M., Polnaszek C. F., Bryant R. G. 25Mg-NMR investigations of the magnesium ion-DNA interaction. Biopolymers. 1982 Mar;21(3):653–664. doi: 10.1002/bip.360210312. [DOI] [PubMed] [Google Scholar]
  24. Rouzina I., Bloomfield V. A. Competitive electrostatic binding of charged ligands to polyelectrolytes: practical approach using the non-linear Poisson-Boltzmann equation. Biophys Chem. 1997 Feb 28;64(1-3):139–155. doi: 10.1016/s0301-4622(96)02231-4. [DOI] [PubMed] [Google Scholar]
  25. Rupprecht A. A wet spinning apparatus and auxiliary equipment suitable for preparing samples of oriented DNA. Biotechnol Bioeng. 1970 Jan;12(1):93–121. doi: 10.1002/bit.260120109. [DOI] [PubMed] [Google Scholar]
  26. Schultz J., Rupprecht A., Song Z., Piskur J., Nordenskiöld L., Lahajnar G. A mechanochemical study of MgDNA fibers in ethanol-water solutions. Biophys J. 1994 Mar;66(3 Pt 1):810–819. doi: 10.1016/s0006-3495(94)80857-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Song Z., Antzutkin O. N., Lee Y. K., Shekar S. C., Rupprecht A., Levitt M. H. Conformational transitions of the phosphodiester backbone in native DNA: two-dimensional magic-angle-spinning 31P-NMR of DNA fibers. Biophys J. 1997 Sep;73(3):1539–1552. doi: 10.1016/S0006-3495(97)78186-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Strauss U. P., Helfgott C., Pink H. Interactions of polyelectrolytes with simple electrolytes. II. Donnan equilibria obtained with DNA in solutions of 1-1 electrolytes. J Phys Chem. 1967 Jul;71(8):2550–2556. doi: 10.1021/j100867a024. [DOI] [PubMed] [Google Scholar]
  29. Young M. A., Ravishanker G., Beveridge D. L. A 5-nanosecond molecular dynamics trajectory for B-DNA: analysis of structure, motions, and solvation. Biophys J. 1997 Nov;73(5):2313–2336. doi: 10.1016/S0006-3495(97)78263-8. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES