Skip to main content

Thank you for visiting nature.com. 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.

  • News & Views
  • Published:

RNA structure

Ribozyme crevices and catalysis

Nature volume 395, pages 548–549 (1998)Cite this article

Since the X-ray crystallographic structure of the hammerhead ribozyme — a catalytic RNA molecule — was solved1 in 1994, the RNA community has been waiting for a view of a second RNA enzyme. We are now rewarded for our patience by not one but two ribozyme structures: a 2.3-Å structure of the ribozyme from the hepatitis delta helper virus (HDV), reported by Ferré-D'Amaré et al.2 on page 567 of this issue; and a 5-Å structure of the group I intron from Tetrahymena thermophila, published by Golden et al.3 in this week's Science. The most striking feature of these RNAs is that they look like enzymes — that is, both have active sites that seem to be preorganized and located in crevices, as we are accustomed to seeing in protein enzymes. This is in marked contrast to the hammerhead ribozyme, which exposes the cleavage site in solution, rather than sequestering it in a cavity, and seems to require a substantial conformational rearrangement to perform its catalytic function1,4,5.

Despite their general similarities, the HDV and Tetrahymena ribozymes are preorganized very differently. The HDV ribozyme is only about one-fifth the size of the Tetrahymena ribozyme, owing to a remarkable intertwining of secondary structural elements in what can be referred to as a ‘double pseudoknot’. The positioning of secondary structure (that is, base-pairing) — which accounts for three-quarters of the HDV residues — within the double pseudoknot establishes the overall position of the helices with respect to each other. This allows a complex, three-dimensional architecture. Several tertiary connections then establish the precise tertiary fold, positioning the functional groups that are required for catalysis, despite the ribozyme's modest size.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

References

  1. Pley, H. W., Flaherty, K. M. & McKay, D. B. Nature 372, 68–74 (1994).

    Article  ADS  CAS  Google Scholar 

  2. Ferré-D'Amaré, A. R., Zhou, K. & Doudna, J. A. Nature 395, 567–574 (1998).

    Article  ADS  Google Scholar 

  3. Golden, B. L., Gooding, A. R., Podell, E. R. & Cech, T. R. Science 282, 259–274 (1998).

    Google Scholar 

  4. McKay, D. B. RNA 2, 395–403 (1996).

    Google Scholar 

  5. Peracchi, A., Karpeisky, A., Maloney, L., Beigelman, L. & Herschlag, D. Biochemistry (in the press).

  6. Cate, J. H. et al. Science 273, 1696–1699 (1996).

    Google Scholar 

  7. Zarrinkar, P. P. & Williamson, J. R. Science 265, 918–924 (1994).

    Google Scholar 

  8. Sclavi, B., Sullivan, M., Chance, M. R., Brenowitz, M. & Woodson, S. A. Science 279, 1940–1942 (1998).

    Google Scholar 

  9. Michel, F., Hanna, M., Green, R., Bartel, D. & Szostak, J. W. Nature 342, 391–395 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Michel, F. & Westhof, E. J. Mol. Biol. 216, 585–610 (1990).

    Google Scholar 

  11. Lehnert, V., Jaeger, L., Michel, F. & Westhof, E. Chem. Biol. 3, 993–1009 (1996).

    Google Scholar 

  12. Been, M. D. & Wickham, G. S. Eur. J. Biochem. 247, 741–753 (1997).

    Google Scholar 

  13. Narlikar, G. J. & Herschlag, D. Annu. Rev. Biochem. 66, 19–59 (1997).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Beckman Center, Stanford University, Stanford, 94305-5307, California, USA

    Daniel Herschlag

Authors
  1. Daniel Herschlag
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Herschlag, D. Ribozyme crevices and catalysis. Nature 395, 548–549 (1998). https://doi.org/10.1038/26864

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/26864

Search

Advanced search

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