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.

  • Review Article
  • Published:

Comparative architecture of transposase and integrase complexes

Nature Structural Biology volume 8, pages 302–307 (2001)Cite this article

An Erratum to this article was published on 01 May 2001

Abstract

Transposases and retroviral integrases promote the movement of DNA segments to new locations within and between genomes. These recombinases function as multimeric protein–DNA complexes. Recent success in solving the crystal structure of a Tn5 transposase–DNA complex provides the first detailed structural information about a member of the transposase/integrase superfamily in its active, DNA-bound state. Here, we summarize the reactions catalyzed by transposases and integrases and review the Tn5 transposase–DNA co-crystal structure. The insights gained from the Tn5 structure and other available structures are considered together with biochemical and genetic data to discuss features that are likely to prove common to the catalytic complexes used by members of this important protein family.

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

Figure 1: A conserved catalytic core.
Figure 2: DNA cleavage and joining reactions catalyzed by transposases.
Figure 3: Transposase–substrate interactions.
Figure 4: Potential target-binding groove in the Tn5 transposase–DNA complex.
Figure 5: Dimer interfaces in other transposase structures.
Figure 6: TnsA from Tn7.

Similar content being viewed by others

Notes

  1. NOTE: A production error resulted in incorrect reference numbering in both the original print and web versions of this Review. On April 25, 2001, the full text and PDF were updated on the web; both are now correct. The correct version was also printed in the May issue as an Erratum . We apologize for any confusion this may have caused.

References

  1. Lander, E.S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

    Article  CAS  Google Scholar 

  2. Yang, W. & Steitz, T.A. Recombining the structures of HIV integrase, RuvC and RNase H. Structure 3, 131–134 (1995).

    Article  CAS  Google Scholar 

  3. Rice, P., Craigie, R. & Davies, D.R. Retroviral integrases and their cousins. Curr. Opin. Struct. Biol. 6, 76–83 (1996).

    Article  CAS  Google Scholar 

  4. Mizuuchi, K. Polynucleotidyl transfer reactions in site-specific DNA recombination. Genes Cells 2, 1–12. (1997).

    Article  CAS  Google Scholar 

  5. Kennedy, A.K., Guhathakurta, A., Kleckner, N. & Haniford, D.B. Tn10 transposition via a DNA hairpin intermediate. Cell 95, 125–134 (1998).

    Article  CAS  Google Scholar 

  6. Bhasin, A., Goryshin, I.Y. & Reznikoff, W.S. Hairpin formation in Tn5 transposition. J. Biol. Chem. 274, 37021–37029 (1999).

    Article  CAS  Google Scholar 

  7. Fugmann, S.D., Lee, A.I., Shockett, P.E., Villey, I.J. & Schatz, D.G. The RAG proteins and V(D)J recombination: complexes, ends, and transposition. Annu. Rev. Immunol. 18, 495–527 (2000).

    Article  CAS  Google Scholar 

  8. Kim, D.R., Park, S.J. & Oettinger, M.A. V(D)J recombination: site-specific cleavage and repair. Mol. Cell 10, 367–374 (2000).

    CAS  Google Scholar 

  9. Sarnovsky, R.J., May, E.W. & Craig, N.L. The Tn7 transposase is a heteromeric complex in which DNA breakage and joining activities are distributed between different gene products. EMBO J. 15, 6348–6361 (1996).

    Article  CAS  Google Scholar 

  10. Davies, D.R., Goryshin, I.Y., Reznikoff, W.S. & Rayment, I. Three-dimensional structure of the Tn5 synaptic complex transposition intermediate. Science 289, 77–85 (2000).

    Article  CAS  Google Scholar 

  11. Steitz, T.A. & Steitz, J.A. A general two-metal ion mechanism for catalytic RNA. Proc. Natl. Acad. Sci. USA 90, 6498–6502 (1993).

    Article  CAS  Google Scholar 

  12. Keck, J.L., Goedken, E.R. & Marqusee, S. Activation/attenuation model for RNase H. A one-metal mechanism with second-metal inhibition. J. Biol. Chem. 273, 34128–34133 (1998).

    Article  CAS  Google Scholar 

  13. Huang, H., Chopra, R., Verdine, G.L. & Harrison, S.C. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282, 1669–1675 (1998).

    Article  CAS  Google Scholar 

  14. Wlodawer, A. Crystal structures of catalytic core domains of retroviral integrases and role of divalent cations in enzymatic activity. Adv. Virus Res. 52, 335–350 (1999).

    Article  CAS  Google Scholar 

  15. Kovall, R.A. & Matthews, B.W. Type II restriction endonucleases: structural, functional and evolutionary relationships. Curr. Opin. Chem. Biol. 3, 578–583 (1999).

    Article  CAS  Google Scholar 

  16. Steitz, T.A. DNA polymerases: structural diversity and common mechanisms. J. Biol. Chem. 274, 17395–17398 (1999).

    Article  CAS  Google Scholar 

  17. Rezsohazy, R., Hallet, B., Delcour, J. & Mahillon, J. The IS4 family of insertion sequences: evidence for a conserved transposase motif. Mol. Microbiol. 9, 1283–1295 (1993).

    Article  CAS  Google Scholar 

  18. Bolland, S. & Kleckner, N. The three chemical steps of Tn10/IS10 transposition involve repeated utilization of a single active site. Cell 84, 223–233 (1996).

    Article  CAS  Google Scholar 

  19. Pribil, P.A. & Haniford, D.B. Substrate recognition and induced DNA deformation by transposase at the target-capture stage of Tn10 transposition. J. Mol. Biol. 303, 145–159 (2000).

    Article  CAS  Google Scholar 

  20. Cai, M. et al. Solution structure of the N-terminal zinc binding domain of HIV-1 integrase. Nature Struct. Biol. 4, 567–577 (1997).

    Article  CAS  Google Scholar 

  21. Eijkelenboom, A.P. et al. The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: a three-helix bundle stabilized by zinc. Curr. Biol. 7, 739–746 (1997).

    Article  CAS  Google Scholar 

  22. Schumacher, S. et al. Solution structure of the Mu end DNA-binding Iβ subdomain of phage Mu transposase: modular DNA recognition by two tethered domains. EMBO J. 16, 7532–7541 (1997).

    Article  CAS  Google Scholar 

  23. Clubb, R.T., Schumacher, S., Mizuuchi, K., Gronenborn, A.M. & Clore, G.M. Solution structure of the Iγ subdomain of the Mu end DNA-binding domain of phage Mu transposase. J. Mol. Biol. 273, 19–25 (1997).

    Article  CAS  Google Scholar 

  24. van Pouderoyen, G., Ketting, R.F., Perrakis, A., Plasterk, R.H. & Sixma, T.K. Crystal structure of the specific DNA-binding domain of Tc3 transposase of C. elegans in complex with transposon DNA. EMBO J. 16, 6044–6054 (1997).

    Article  CAS  Google Scholar 

  25. Williams, T.L., Jackson, E.L., Carritte, A. & Baker, T.A. Organization and dynamics of the Mu transpososome: recombination by communication between two active sites. Genes Dev. 13, 2725–2737 (1999).

    Article  CAS  Google Scholar 

  26. Savilahti, H. & Mizuuchi, K. Mu transpositional recombination: donor DNA cleavage and strand transfer in trans by the Mu transposase. Cell 85, 271–280 (1996).

    Article  CAS  Google Scholar 

  27. Namgoong, S.Y. & Harshey, R.M. The same two monomers within a MuA tetramer provide the DDE domains for the strand cleavage and strand transfer steps of transposition. EMBO J. 17, 3775–3785 (1998).

    Article  CAS  Google Scholar 

  28. Aldaz, H., Schuster, E. & Baker, T.A. The interwoven architecture of the Mu transposase couples DNA synapsis to catalysis. Cell 85, 257–269 (1996).

    Article  CAS  Google Scholar 

  29. Haren, L., Ton-Hoang, B. & Chandler, M. Integrating DNA: transposases and retroviral integrases. Annu. Rev. Microbiol. 53, 245–81 (1999).

    Article  CAS  Google Scholar 

  30. Chen, J.C. et al. Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc. Natl. Acad. Sci. USA 97, 8233–8238 (2000).

    Article  CAS  Google Scholar 

  31. Chen, Z. et al. X-ray structure of simian immunodeficiency virus integrase containing the core and C-terminal domain (residues 50–293) — an initial glance of the viral DNA binding platform. J. Mol. Biol. 296, 521–533 (2000).

    Article  CAS  Google Scholar 

  32. Yang, Z.N., Mueser, T.C., Bushman, F.D. & Hyde, C.C. Crystal structure of an active two-domain derivative of Rous sarcoma virus integrase. J. Mol. Biol. 296, 535–548 (2000).

    Article  CAS  Google Scholar 

  33. Asante-Appiah, E. & Skalka, A.M. HIV-1 integrase: structural organization, conformational changes, and catalysis. Adv. Virus Res. 52, 351–369 (1999).

    Article  CAS  Google Scholar 

  34. Esposito, D. & Craigie, R. HIV integrase structure and function. Adv. Virus Res. 52, 319–333 (1999).

    Article  CAS  Google Scholar 

  35. Heuer, T.S. & Brown, P.O. Photo-crosslinking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase–DNA complex. Biochemistry 37, 6667–6678 (1998).

    Article  CAS  Google Scholar 

  36. Lavoie, B.D., Chan, B.S., Allison, R.G. & Chaconas, G. Structural aspects of a higher order nucleoprotein complex: induction of an altered DNA structure at the Mu–host junction of the Mu type 1 transpososome. EMBO J. 10, 3051–3059 (1991).

    Article  CAS  Google Scholar 

  37. Rice, P. & Mizuuchi, K. Structure of the bacteriophage Mu transposase core: a common structural motif for DNA transposition and retroviral integration. Cell 82, 209–220 (1995).

    Article  CAS  Google Scholar 

  38. Krementsova, E., Giffin, M.J., Pincus, D. & Baker, T.A. Mutational analysis of the Mu transposase. Contributions of two distinct regions of domain II to recombination. J. Biol. Chem. 273, 31358–31365 (1998).

    Article  CAS  Google Scholar 

  39. Namgoong, S.Y. et al. Mutational analysis of domain IIβ of bacteriophage Mu transposase: domains IIα and IIβ belong to different catalytic complementation groups. J. Mol. Biol. 275, 221–232 (1998).

    Article  CAS  Google Scholar 

  40. Turlan, C. & Chandler, M. Playing second fiddle: second-strand processing and liberation of transposable elements from donor DNA. Trends Microbiol. 8, 268–274 (2000).

    Article  CAS  Google Scholar 

  41. Hickman, A.B. et al. Unexpected structural diversity in DNA recombination: the restriction endonuclease connection. Mol. Cell 5, 1025–1034 (2000).

    Article  CAS  Google Scholar 

  42. Kennedy, A.K., Haniford, D.B. & Mizuuchi, K. Single active site catalysis of the successive phosphoryl transfer steps by DNA transposases: insights from phosphorothioate stereoselectivity. Cell 101, 295–305 (2000).

    Article  CAS  Google Scholar 

  43. Stellwagen, A.E. & Craig, N.L. Mobile DNA elements: controlling transposition with ATP-dependent molecular switches. Trends Biochem. Sci. 23, 486–490 (1998).

    Article  CAS  Google Scholar 

  44. Lee, M.S. & Craigie, R. A previously unidentified host protein protects retroviral DNA from autointegration. Proc. Natl. Acad. Sci. USA 95, 1528–1533 (1998).

    Article  CAS  Google Scholar 

  45. Carson, M. Ribbons. Macromol. Crystallogr. B 277, 493–505 (1997).

    Article  CAS  Google Scholar 

  46. Lavoie, B.D. & Chaconas, G. Transposition of phage Mu DNA. Curr. Top. Microbiol. Immunol. 204, 83–102 (1996).

    CAS  PubMed  Google Scholar 

  47. Kleckner, N., Chalmers, R.M., Kwon, D., Sakai, J. & Bolland, S. Tn10 and IS10 transposition and chromosome rearrangements: mechanism and regulation in vivo and in vitro. Curr. Top. Microbiol. Immunol. 204, 49–82 (1996).

    CAS  PubMed  Google Scholar 

  48. Reznikoff, W.S. et al. Tn5: A molecular window on transposition. Biochem. Biophys. Res. Commun. 266, 729–734. (1999).

    Article  CAS  Google Scholar 

  49. Craig, N.L. Transposon Tn7. Curr. Top. Microbiol. Immunol. 204, 27–48. (1996).

    CAS  PubMed  Google Scholar 

  50. Bolland, S. & Kleckner, N. The two single-strand cleavages at each end of Tn10 occur in a specific order during transposition. Proc. Natl. Acad. Sci. USA 92, 7814–7818 (1995).

    Article  CAS  Google Scholar 

  51. Nicholls, A., Sharp, K.A. & Honig, B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11, 281–296 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank B. Burton, I. Goldhaber-Gordon, L. Roldan, T. Sokolsky, T. Williams, K. Swinger and C. Correll for helpful comments on the manuscript. Work on transposases in T.A.B.'s lab is supported by the NIH and in P.A.R.'s lab by the University of Chicago Faculty Research Fund. T.A.B. is an employee of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, 60637, Illinois, USA

    Phoebe A. Rice

  2. Department of Biology and the Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, 02139-4307, Massachusetts, USA

    Tania A. Baker

Authors
  1. Phoebe A. Rice
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tania A. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Phoebe A. Rice.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rice, P., Baker, T. Comparative architecture of transposase and integrase complexes. Nat Struct Mol Biol 8, 302–307 (2001). https://doi.org/10.1038/86166

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/86166

This article is cited by

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