Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1994 Dec 11;22(24):5447–5455. doi: 10.1093/nar/22.24.5447

Structural properties of the [d(G3T4G3)]2 quadruplex: evidence for sequential syn-syn deoxyguanosines.

G D Strahan 1, R H Shafer 1, M A Keniry 1
PMCID: PMC332095  PMID: 7816637

Abstract

Two-dimensional 1H NMR studies on the dimeric hairpin quadruplex formed by d(G3T4G3) in the presence of either NaCl or KCl are presented. In the presence of either salt, the quadruplex structure is characterized by half the guanine nucleosides in the syn conformation about the glycosidic bond, the other half in the anti conformation, as reported for other similar sequences. However, 1H NOESY and 1H-31P heteronuclear correlation experiments demonstrate that the deoxyguanosines do not strictly alternate between syn and anti along individual strands. Thus we find the following sequences with regard to glycosidic bond conformation: 5'-G1SG2SG3AT4AT5A-T6AT7AG8SG9AG10A-3' and 5'-G11SG12AG13AT14AT1 5AT16AT17AG18SG19SG20A-3', where S and A denote syn and anti, respectively. This represents the first experimental evidence for a nucleic acid structure containing two sequential nucleosides in the syn conformation. The stacking interactions of the resulting quadruplex quartets and their component bases have been evaluated using unrestrained molecular dynamics calculations and energy component analysis. These calculations suggest that the sequential syn-syn/anti-anti and syn-anti quartet stacks are almost equal in energy, whereas the anti-syn stack, which is not present in our structure, is energetically less favorable by about 4 kcal/mol. Possible reasons for this energy difference and its implications for the stability of quadruplex structures are discussed.

Full text

PDF
5447

Selected References

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

  1. Aboul-ela F., Murchie A. I., Lilley D. M. NMR study of parallel-stranded tetraplex formation by the hexadeoxynucleotide d(TG4T). Nature. 1992 Nov 19;360(6401):280–282. doi: 10.1038/360280a0. [DOI] [PubMed] [Google Scholar]
  2. Arnott S., Selsing E. Letter: The structure of polydeoxyguanylic acid with polydeoxycytidylic acid. J Mol Biol. 1974 Sep 15;88(2):551–552. doi: 10.1016/0022-2836(74)90502-6. [DOI] [PubMed] [Google Scholar]
  3. Blackburn E. H. Structure and function of telomeres. Nature. 1991 Apr 18;350(6319):569–573. doi: 10.1038/350569a0. [DOI] [PubMed] [Google Scholar]
  4. Cheong C., Moore P. B. Solution structure of an unusually stable RNA tetraplex containing G- and U-quartet structures. Biochemistry. 1992 Sep 15;31(36):8406–8414. doi: 10.1021/bi00151a003. [DOI] [PubMed] [Google Scholar]
  5. GELLERT M., LIPSETT M. N., DAVIES D. R. Helix formation by guanylic acid. Proc Natl Acad Sci U S A. 1962 Dec 15;48:2013–2018. doi: 10.1073/pnas.48.12.2013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gupta G., Garcia A. E., Guo Q., Lu M., Kallenbach N. R. Structure of a parallel-stranded tetramer of the Oxytricha telomeric DNA sequence dT4G4. Biochemistry. 1993 Jul 20;32(28):7098–7103. doi: 10.1021/bi00079a005. [DOI] [PubMed] [Google Scholar]
  7. Hardin C. C., Henderson E., Watson T., Prosser J. K. Monovalent cation induced structural transitions in telomeric DNAs: G-DNA folding intermediates. Biochemistry. 1991 May 7;30(18):4460–4472. doi: 10.1021/bi00232a013. [DOI] [PubMed] [Google Scholar]
  8. Henderson E., Hardin C. C., Walk S. K., Tinoco I., Jr, Blackburn E. H. Telomeric DNA oligonucleotides form novel intramolecular structures containing guanine-guanine base pairs. Cell. 1987 Dec 24;51(6):899–908. doi: 10.1016/0092-8674(87)90577-0. [DOI] [PubMed] [Google Scholar]
  9. Jin R. Z., Breslauer K. J., Jones R. A., Gaffney B. L. Tetraplex formation of a guanine-containing nonameric DNA fragment. Science. 1990 Oct 26;250(4980):543–546. doi: 10.1126/science.2237404. [DOI] [PubMed] [Google Scholar]
  10. Jin R., Gaffney B. L., Wang C., Jones R. A., Breslauer K. J. Thermodynamics and structure of a DNA tetraplex: a spectroscopic and calorimetric study of the tetramolecular complexes of d(TG3T) and d(TG3T2G3T). Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8832–8836. doi: 10.1073/pnas.89.18.8832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kang C., Zhang X., Ratliff R., Moyzis R., Rich A. Crystal structure of four-stranded Oxytricha telomeric DNA. Nature. 1992 Mar 12;356(6365):126–131. doi: 10.1038/356126a0. [DOI] [PubMed] [Google Scholar]
  12. Liu Z., Frantz J. D., Gilbert W., Tye B. K. Identification and characterization of a nuclease activity specific for G4 tetrastranded DNA. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3157–3161. doi: 10.1073/pnas.90.8.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Scaria P. V., Shire S. J., Shafer R. H. Quadruplex structure of d(G3T4G3) stabilized by K+ or Na+ is an asymmetric hairpin dimer. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10336–10340. doi: 10.1073/pnas.89.21.10336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schultze P., Smith F. W., Feigon J. Refined solution structure of the dimeric quadruplex formed from the Oxytricha telomeric oligonucleotide d(GGGGTTTTGGGG). Structure. 1994 Mar 15;2(3):221–233. doi: 10.1016/s0969-2126(00)00023-x. [DOI] [PubMed] [Google Scholar]
  15. Sen D., Gilbert W. A sodium-potassium switch in the formation of four-stranded G4-DNA. Nature. 1990 Mar 29;344(6265):410–414. doi: 10.1038/344410a0. [DOI] [PubMed] [Google Scholar]
  16. Sklenár V., Miyashiro H., Zon G., Miles H. T., Bax A. Assignment of the 31P and 1H resonances in oligonucleotides by two-dimensional NMR spectroscopy. FEBS Lett. 1986 Nov 10;208(1):94–98. doi: 10.1016/0014-5793(86)81539-3. [DOI] [PubMed] [Google Scholar]
  17. Smith F. W., Feigon J. Quadruplex structure of Oxytricha telomeric DNA oligonucleotides. Nature. 1992 Mar 12;356(6365):164–168. doi: 10.1038/356164a0. [DOI] [PubMed] [Google Scholar]
  18. Smith F. W., Feigon J. Strand orientation in the DNA quadruplex formed from the Oxytricha telomere repeat oligonucleotide d(G4T4G4) in solution. Biochemistry. 1993 Aug 24;32(33):8682–8692. doi: 10.1021/bi00084a040. [DOI] [PubMed] [Google Scholar]
  19. Smith F. W., Lau F. W., Feigon J. d(G3T4G3) forms an asymmetric diagonally looped dimeric quadruplex with guanosine 5'-syn-syn-anti and 5'-syn-anti-anti N-glycosidic conformations. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10546–10550. doi: 10.1073/pnas.91.22.10546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sundquist W. I., Heaphy S. Evidence for interstrand quadruplex formation in the dimerization of human immunodeficiency virus 1 genomic RNA. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3393–3397. doi: 10.1073/pnas.90.8.3393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wang K. Y., McCurdy S., Shea R. G., Swaminathan S., Bolton P. H. A DNA aptamer which binds to and inhibits thrombin exhibits a new structural motif for DNA. Biochemistry. 1993 Mar 2;32(8):1899–1904. doi: 10.1021/bi00059a003. [DOI] [PubMed] [Google Scholar]
  22. Wang Y., Jin R., Gaffney B., Jones R. A., Breslauer K. J. Characterization by 1H NMR of glycosidic conformations in the tetramolecular complex formed by d(GGTTTTTGG). Nucleic Acids Res. 1991 Sep 11;19(17):4619–4622. doi: 10.1093/nar/19.17.4619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wang Y., Patel D. J. Guanine residues in d(T2AG3) and d(T2G4) form parallel-stranded potassium cation stabilized G-quadruplexes with anti glycosidic torsion angles in solution. Biochemistry. 1992 Sep 8;31(35):8112–8119. doi: 10.1021/bi00150a002. [DOI] [PubMed] [Google Scholar]
  24. Wang Y., Patel D. J. Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex. Structure. 1993 Dec 15;1(4):263–282. doi: 10.1016/0969-2126(93)90015-9. [DOI] [PubMed] [Google Scholar]
  25. Wang Y., de los Santos C., Gao X. O., Greene K., Live D., Patel D. J. Multinuclear nuclear magnetic resonance studies of Na cation-stabilized complex formed by d(G-G-T-T-T-T-C-G-G) in solution. Implications for G-tetrad structures. J Mol Biol. 1991 Dec 5;222(3):819–832. doi: 10.1016/0022-2836(91)90513-6. [DOI] [PubMed] [Google Scholar]
  26. Weisman-Shomer P., Fry M. QUAD, a protein from hepatocyte chromatin that binds selectively to guanine-rich quadruplex DNA. J Biol Chem. 1993 Feb 15;268(5):3306–3312. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES