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Anomalous Conformations of RNA Constituents : 2D NMR and Calculational Studies

  • Cornelis Altona
Part of the NATO ASI Series book series (NSSA, volume 110)

Abstract

Short single-stranded RNA fragments normally display a strong tendency to favour a right-handed helical conformation. Relatively small changes in enthalpy and/or entropy of stacking, induced by minor structural variations may cause a large difference in stacking behaviour in aqueous solution, but do not appear to affect the detailed geometry of the stacked state. Recently developed NMR methods that allow for a determination of the sugar-phosphate backbone geometry along β (O5’-C5’), γ (C5’-C4’), δ (C4’-C3’), and ε (C3’-O3’) are surveyed. At the level of trimers and higher oligomers conformational transmission factors, such as next-nearest-neighbour interactions, may come into play. For example, the trimer U-A¯-U (A¯ = m2 6A) behaves in a fashion that can be predicted from the known stacking properties of its dimer constituents U-A¯ and A¯-U, whereas the trimer A¯-U-A¯ behaves in an entirely different way. In the latter compound the two purines engage in a 1-3 stacking interaction. At the same time the central pyrimidine residue is pushed outside the purine-purine interaction zone (bulge-out).

Several interesting properties of bulges have come to light: (i) a longer alternating pu-py sequence displays multiple bulges, witness A¯-U-A¯-U-A¯; (ii) a strong stacking interaction at its 3’-end does not affect the bulge, for example in A¯-U-A¯-U; (iii) in contrast, the bulge is abandoned in favour of a normal right-handed stacking pattern by a strong stacking interaction at its 5’-end: A¯-A¯-U-A¯; (iv) a self-complementary alternating pu-py sequence, e.g. (A-U)3, is able to convert from a bulged single strand at elevated temperatures into a regular A-type duplex at low temperature. Thus, bulge-out structures may occur either in loops or under conditions where a duplex is forced to open up.

Another interesting conformation is shown by the 3A’-terminal C¯-A¯ in C¯-C¯-A¯ (C¯ = m2 4C), a chemically modified 3’-acceptor of tRNAs. In contrast to the usual right-handed parallel stacking pattern favoured by the C¯-C¯ part, the 3’-terminal A¯ residue prefers to adopt a left-handed antiparallel stacking.

With the aid of molecular-mechanics calculations (AMBER program) various plausible A-U-A and C-C-A models could be generated.

Keywords

Circular Dichroism Torsion Angle Nuclear Overhauser Effect Single Helix Backbone Angle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    C. Altona, Reel. Trav. Chim. Pays-Bas 101:413 (1982).CrossRefGoogle Scholar
  2. 2.
    P. P. Lankhorst, C. A. G. Haasnoot, C. Erkelens, and C. Altona, J. Biomol. Struct. Dyns. 1:1387 (1984).Google Scholar
  3. 3.
    P. P. Lankhorst, C. A. G. Haasnoot, C. Erkelens, and C. Altona, Nucleic Acids Res. 12:5419 (1984).CrossRefGoogle Scholar
  4. 4.
    P. P. Lankhorst, C. A. G. Haasnoot, C. Erkelens, H. P. Westerink, G. A. van der Marel, J. H. van Boom, and C. Altona, Nucleic Acids Res. 13:927 (1985).CrossRefGoogle Scholar
  5. 5.
    C. A. G. Haasnoot, and C. Altona, Nucleic Acids Res. 6:1135 (1979).CrossRefGoogle Scholar
  6. 6.
    J. T. Powell, E. G. Richards, and W. B. Gratzer, Biopolymers 11:235 (1972).CrossRefGoogle Scholar
  7. 7.
    M. J. Lowe, and J. A. Schellman, J. Mol. Biol. 65:91 (1972).CrossRefGoogle Scholar
  8. 8.
    C. S. M. Olsthoorn, C. A. G. Haasnoot, and C. Altona, Eur. J. Biochem. 106:85 (1980).CrossRefGoogle Scholar
  9. 9.
    C. S. M. Olsthoorn, L. J. Bostelaar, J. H. van Boom, and C. Altona, Eur. J. Biochem. 112:95 (1980).CrossRefGoogle Scholar
  10. 1O.
    C. S. M. Olsthoorn, J. Doornbos, H. P. M. de Leeuw, and C. Altona, Eur. J. Biochem. 125:367 (1982).CrossRefGoogle Scholar
  11. 11.
    C. Altona, A. J. Hartel, C. S. M. Olsthoorn, H. P. M. de Leeuw, and C. A. G. Haasnoot, in: “Nuclear Magnetic Resonance Spectroscopy in Molecular Biology”, B. Pullman, ed. p. 87, D. Reidel Publishing Co. Dordrecht, Holland (1978).CrossRefGoogle Scholar
  12. 12.
    A. J. Hartel, P. P. Lankhorst, and C. Altona, Eur. J. Biochem. 129:343 (1982).CrossRefGoogle Scholar
  13. 13.
    P. P. Lankhorst, C. Erkelens, C. A. G. Haasnoot, and C. Altona, Nucleic Acids Res. 11:7215 (1983).CrossRefGoogle Scholar
  14. 14.
    P. O. P. Ts’o, in: “Basic Principles of Nucleic Acid Chemistry”, P. O. P. Ts’o ed., Academic Press, New York (1974).Google Scholar
  15. 15.
    C. Altona, in: “Structure and Conformation of Nucleic Acids and Protein-Nucleic Acid Interactions”, M. Sundaralingam and S. T. Rao, eds, p. 613, University Park Press, Baltimore (1975).Google Scholar
  16. 16.
    D. M. Gray, and I. Tinoco jr, Biopolymers 11:1235 (1972).CrossRefGoogle Scholar
  17. 17.
    D. Frechet and J. Gabarro-Arpa, Biochim. Biophys. Acta 609:1 (1980).Google Scholar
  18. 18.
    IUPAC-IUB Joint Commission on Biochemical Nomenclature, Eur. J. Biochem. 131:9 (1983)CrossRefGoogle Scholar
  19. 19.
    W. Klyne, and V. Prelog, Experientia 16:521 (1960).CrossRefGoogle Scholar
  20. 2O.
    C. Altona, and M. Sundaralingam, J. Am. Chem. Soc. 94:8205 (1973).CrossRefGoogle Scholar
  21. 21.
    C. Altona, and M. Sundaralingam, J. Am. Chem. Soc. 95:2333 (1973).CrossRefGoogle Scholar
  22. 22.
    H. P. M. de Leeuw, C. A. G. Haasnoot, and C. Altona, Isr. J. Chem. 20:108 (1980).Google Scholar
  23. 23.
    F. A. A. M. de Leeuw, P. N. van Kampen, C. Altona, E. Diez, and A. L. Esteban, J. Mol. Struct. 125:67 (1984).CrossRefGoogle Scholar
  24. 24.
    C. A. G. Haasnoot, F. A. A. M. de Leeuw, and C. Altona, Tetrahedron 36:2783 (1980).CrossRefGoogle Scholar
  25. 25.
    C. A. G. Haasnoot, F. A. A. M. de Leeuw, and C. Altona, Bull. Soc. Chim. Belg. 89:125 (1980)CrossRefGoogle Scholar
  26. 26.
    C. A. G. Haasnoot, F. A. A. M. de Leeuw, H. P. M. de Leeuw, and C. Altona, Org. Magn. Reson. 15:43 (1981).CrossRefGoogle Scholar
  27. 27.
    A. J. Hartel, G. Wille, J. H. van Boom, and C., Altona, Nucleic Acids Res. 9:1405 (1981).CrossRefGoogle Scholar
  28. 28.
    C. A. G. Haasnoot, F. A. A. M. de Leeuw, H. P. M. de Leeuw, and C. Altona, Biopolymers 20:1211 (1981).CrossRefGoogle Scholar
  29. 29.
    F. A. A. M. de Leeuw, and C. Altona, J. Chem. Soc. Perkin II, 375 (1982).Google Scholar
  30. 30.
    F. A. A. M. de Leeuw, and C. Altona, J. Comp. Chem. 4:428 (1983).CrossRefGoogle Scholar
  31. 31.
    F. A. A. M. de Leeuw, and C. Altona, Int. J. Pept. Protein Res. 20:120 (1982).CrossRefGoogle Scholar
  32. 32.
    J.-R. Mellema, A. K. Jellema, C. A. G. Haasnoot, J. H. van Boom, and C. Altona, Eur. J. Biochem. 141:165 (1984).CrossRefGoogle Scholar
  33. 33.
    J.-R. Mellema, J. M. L. Pieters, G. A. van der Marel, J. H. van Boom, C. A. G. Haasnoot, and C. Altona, Eur. J. Biochem. 143:285 (1984).CrossRefGoogle Scholar
  34. 34.
    F. A. A. M. de Leeuw and C. Altona, Quant. Chem. Progr. Exch. No 463 (1983).Google Scholar
  35. 35.
    F. A. A. M. de Leeuw, A. A. van Beuzekom, and C. Altona, J. Comp. Chem. 4:438 (1983).CrossRefGoogle Scholar
  36. 36.
    S. Arnott, P. J. Campbell Smith, and R. Chandrasekan, in: “CRC Handbook of Biochemistry and Molecular Biology”, p. 411 (1975).Google Scholar
  37. 37.
    C.-H. Lee and I. Tinoco Jr, Biophys. Chem. 11:283 (1980).CrossRefGoogle Scholar
  38. 38.
    P. P. Lankhorst, C. M. Groeneveld, G. Wille, J. H. van Boom, C. A. G. Haasnoot, and C. Altona, Recl. Trav. Chim. Pays-Bas 101:253 (1982).CrossRefGoogle Scholar
  39. 39.
    P. P. Lankhorst, G. Wille, J. H. van Boom, C. A. G. Haasnoot, and C. Altona, Nucleic Acids Res. 11:2839 (1983).CrossRefGoogle Scholar
  40. 40.
    P. P. Lankhorst, G. A. van der Marel, G. Wille, J. H. van Boom, and C. Altona, Nucleic Acids Res. 13:3317 (1985).CrossRefGoogle Scholar
  41. 41.
    C. M. Groeneveld, P. P. Lankhorst, and C. Altona, unpublished observations.Google Scholar
  42. 42.
    J. Doornbos, H. P. M. de Leeuw, C. S. M. Olsthoorn, G. Wille, H. P. Westerink, J. H. van Boom, and C. Altona, Nucleic Acids Res. 11:7517 (1983).CrossRefGoogle Scholar
  43. 43.
    P. Kollman, P. Weiner, and A. Dearing, Biopolymers 20:2583 (1981)CrossRefGoogle Scholar
  44. 44.
    S. J. Weiner, P. A. Kollman, D. A. Case, U. Chandra Singh, C. Ghio, G. Alagona, S. Profeta Jr, and P. Weiner, J. Am. Chem. Soc. 106:765 (1984).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Cornelis Altona
    • 1
  1. 1.Gorlaeus Laboratory of the State UniversityLeidenThe Netherlands

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