Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A three–dimensional model of the Rev–binding element of HIV–1 derived from analyses of aptamers


Coordinated variations in the sequence of the Rev–binding element of HIV–1, identified by in vitro genetic selections, have been used as distance and conformational constraints for molecular modelling. Three–dimensional models of the wild–type Rev–binding element and several, evolved RNA ligands (aptamers) have been constructed. These models demonstrate that non–Watson–Crick pairings open the major groove allowing access of an α–helical peptide from Rev, and explain why some selected RNA sequences can bind Rev more tightly than others.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout


  1. Cullen, B.R. & Greene, W.C. Regulatory pathways governing HIV-1 replication. Cell 58, 423–426 (1989).

    Article  CAS  Google Scholar 

  2. Cullen, B.R. & Malim, M.H. The HIV-1 protein: prototype of a novel class of eukaryotic post-transcriptional regulators. Trends biochem. Sci. 16, 346–350 (1991).

    Article  CAS  Google Scholar 

  3. Zapp, M.L. & Green, M.R. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature 342, 714–716 (1989).

    Article  CAS  Google Scholar 

  4. Tan, R., Chen, L., Buettner, J.A., Hudson, D. & Frankel, A.D. RNA recognition by an isolated α-helix. Cell 73, 1031–1040 (1993).

    Article  CAS  Google Scholar 

  5. Kjems, J., Calnan, B.J., Frankel, A.D. & Sharp, P.A. Specific binding of a basic peptide from HIV-1 Rev. EMBO J., 11, 1119–1129 (1992).

    Article  CAS  Google Scholar 

  6. Gait, M.J. & Karn, J. RNA recognition by the human immunodeficiency virus Tat and Rev proteins. Trends biochem. Sci. 18, 255–259 (1993).

    Article  CAS  Google Scholar 

  7. Giver, L., Bartel, D., Zapp, M., Pawul, A., Green, M. & Ellington, A.D. Selective optimization of the Rev-binding element of HIV-1. Nucl. Acids Res. 21, 5509–5516 (1993).

    Article  CAS  Google Scholar 

  8. Major, F., Turcotte, M., Gautheret, D., Lapalme, G., Fillion, E. & Cedergren, R. The combination of symbolic and numerical computation for three-dimensional modeling of RNA. Science 253, 1255–1260 (1991).

    Article  CAS  Google Scholar 

  9. Gautheret, D., Major, F. & Cedergren, F. Modeling the three-dimensional structure of RNA using discrete nucleotide conformational sets. J. molec. Biol. 229, 1049–1064 (1993).

    Article  CAS  Google Scholar 

  10. Le, S.-Y., Malim, M.H., Cullen, B.R. & Maizel, J.V. A highly conserved RNA folding region coincident with the Rev responsive element of primate immunodeficiency viruses. Nucl. Acids Res. 18, 1613–1623 (1990).

    Article  CAS  Google Scholar 

  11. Bartel, D.P., Zapp, M.L., Green, M.R. & Szostak, J.W. HIV-1 Rev regulation involves recognition of non-Watson-Crick base-pairs in viral RNA. Cell 67, 529–536 (1991).

    Article  CAS  Google Scholar 

  12. Giver, L., Bartel, D.P., Zapp, M.L., Green, M.R. & Ellington, A.D. Selection and design of high-affinity RNA ligands for HIV-1 Rev. Gene (in the press).

  13. Holland, S.K., Chavez, M., Gerstberger, S. & Venkatesan, S. A specific sequence with a bulged guanosine residue(s) in a stem-bulge-stem structure of rev-responsive element RNA is required for trans activation by human immunodeficiency virus type 1 rev. J. Virol. 66, 3699–3706 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Couture, S. et al. Mutational analysis of conserved nucleotides in a self-splicing group I intron. J. molec. Biol. 215, 345–358 (1990).

    Article  CAS  Google Scholar 

  15. Iwai, S., Pritchard, C., Mann, D.A., Karn, J. & Gait, M.J. Recognition of the high affinity binding site in rev-responsive element RNA by the human immunodeficiency virus type-1 Rev protein. Nucl. Acids Res. 20, 6465–6472 (1992).

    Article  CAS  Google Scholar 

  16. Roy, S., Sklenar, V., Apella, E. & Cohen, J.S. Conformational perturbation due to an extra adenosine in a self-complementary oligodeoxynucleotide duplex. Biopolymers 26, 2041–2052 (1987).

    Article  CAS  Google Scholar 

  17. Woodson, S.A. & Crothers, D.M. Structural model for an oligonucleotide containing a bulged guanosine by NMR and energy minimization. Biochemistry 27, 3130–3141 (1988).

    Article  CAS  Google Scholar 

  18. Rould, M.A., Perona, D.S., Soll, D. & Steitz, T.A. Structure of E coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP at 2.8 Å resolution. Science 246, 1135–1142 (1989).

    Article  CAS  Google Scholar 

  19. Weiner, S.J. et al. A new force field for molecular mechanical simulation of nucleic acids and proteins. J. Am. chem. Soc. 106, 765–784 (1984).

    Article  CAS  Google Scholar 

  20. Weiner, S.J., Kollman, P.A., Nguyen, D.T. & Case, D.A. An all atom forcefield for simulations of proteins and nucleic acid. J. comp. Chem. 7, 230–252 (1986).

    Article  CAS  Google Scholar 

  21. Cheong, C., Varani, G. & Tinoco, I. Solution structure of an unusually stable RNA hairpin, 5′ GGAC(UUCG)GUCC. Nature 346, 680–682 (1990).

    Article  CAS  Google Scholar 

  22. Malim, M.H., Hauber, J., Le, S.-Y., Maizel, J.V. & Cullen, B.R. The HIV-1 Rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338, 254–257 (1989).

    Article  CAS  Google Scholar 

  23. Saenger, W. Principles of Nucleic Acid Structure. (New York, Springer-Verlag, 1984).

    Book  Google Scholar 

  24. Benedetti, E., Morelli, G., Nemethy, G. & Scheraga, A. Statistical and energetic analysis of side-chain conformations in oligopeptides. Int. J. Pept. Prot. Res. 22, 1–15 (1983).

    Article  CAS  Google Scholar 

  25. McGregor, M.J., Islam, S.A. & Sternberg, J.E. Analysis of the relationship between side-chain conformation and secondary structure in globular proteins. J. molec. Biol. 198, 295–310 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Leclerc, F., Cedergren, R. & Ellington, A. A three–dimensional model of the Rev–binding element of HIV–1 derived from analyses of aptamers. Nat Struct Mol Biol 1, 293–300 (1994).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing