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The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I

Nature Structural Biology volume 7, pages 23–27 (2000)Cite this article

Abstract

Pseudouridine synthases catalyze the isomerization of specific uridines to pseudouridine in a variety of RNAs, yet the basis for recognition of the RNA sites or how they catalyze this reaction is unknown. The crystal structure of pseudouridine synthase I from Escherichia coli, which, for example, modifies positions 38, 39 and/or 40 in tRNA, reveals a dimeric protein that contains two positively charged, RNA-binding clefts along the surface of the protein. Each cleft contains a highly conserved aspartic acid located at its center. The structural domains have a topological similarity to those of other RNA-binding proteins, though the mode of interaction with tRNA appears to be unique. The structure suggests that a dimeric enzyme is required for binding transfer RNA and subsequent pseudouridine formation.

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Figure 1: The central role of Asp 60 in ΨS I mechanism and structure.
Figure 2: The central role of the catalytic Asp 60 in the ΨS I monomer.
Figure 3: A similar fold to a common RNA-binding domain.
Figure 4: A model for binding the global structure of tRNA.

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References

  1. Huang, L.X., et al. Biochemistry 37, 15,951– 15,957 (1998).

    Article  CAS  Google Scholar 

  2. Gu, X., Yu, M., Ivanetich, K.M. & Santi, D.V. Biochemistry 37, 339–343 (1998).

    Article  CAS  Google Scholar 

  3. Wrzensinski, J., Nurse, K., Bakin, A., Lane, B.G. & Ofengand, J. RNA 1, 437–448 (1995).

    Google Scholar 

  4. Motorin, Y. et al. RNA 4, 856–869 (1998).

    Article  CAS  Google Scholar 

  5. Grosjean, H. & Benne, R. Modification and editing of RNA. (ASM Press, Washington, DC; 1998).

    Book  Google Scholar 

  6. Rozenski, J., Crain, P.F. & McCloskey, J.A. Nucleic Acids Res. 27, 196– 197 (1999).

    Article  CAS  Google Scholar 

  7. Bakin, A., Lane, B.G. & Ofengand, J. Biochemistry 33, 13,475– 13,483 (1994).

    Article  CAS  Google Scholar 

  8. Huang, L., Pookanjanatavip, M., Gu, X. & Santi, D.V. Biochemistry 37, 344–351 (1998).

    Article  CAS  Google Scholar 

  9. Gu, X, Liu, Y. & Santi, D.V. Proc. Natl. Acad. Sci. USA, in the press ( 1999).

  10. Conrad, J., Niu, L.H., Rudd, K., Lane, B.G. & Ofengand, J. RNA 5, 751–763 (1999).

    Article  CAS  Google Scholar 

  11. Ramamurthy, V., Swann, S.L., Paulson., J.L., Spedaliere, C.J. & Mueller, E.G. J. Biol. Chem. 274, 22225–22230 (1999).

    Article  CAS  Google Scholar 

  12. Foster, P.G., Huang, L., Santi, D. V & Stroud, R.M. FASEB J. 11, A862 (1997).

    Google Scholar 

  13. Corollo, D. et al. Acta Crystallogr. D 55, 302– 304 (1999).

    Article  CAS  Google Scholar 

  14. Oubridge, C., Ito, N., Evans, P.R., Teo, C.H. & Nagai, K. Nature 372, 432– 438 (1994).

    Article  CAS  Google Scholar 

  15. Allain, F.H., Howe, P.W., Neuhaus, D. & Varani, G. EMBO J. 16, 5,764–5,774 (1997).

    Article  CAS  Google Scholar 

  16. Kenan, D.J., Query, C.C. & Keene, J.D. Trends Biochem. Sci. 16, 214 –220 (1991).

    Article  CAS  Google Scholar 

  17. Jones, S. & Thornton, J.M. Proc. Natl. Acad. Sci. USA 93, 13–20 (1996).

    Article  CAS  Google Scholar 

  18. Arena, F., Ciliberto, G., Ciampi, S. & Cortese, R. Nucleic Acids Res. 5, 4,523–4,536 (1978).

    Article  CAS  Google Scholar 

  19. Lecointe, F., et al., J. Biol. Chem. 273, 1,316– 1,323 (1998).

    Article  CAS  Google Scholar 

  20. Van Duyne, G.D., Standaert, R.F., Karplus, P.A., Schreiber, S.L. & Clardy, J. J. Mol. Biol. 229, 105–124 (1993).

    Article  CAS  Google Scholar 

  21. Otwinowski, Z. & Minor, W. Methods Enzymol. 276, 307–326 ( 1997).

    Article  CAS  Google Scholar 

  22. Furey, W. & Swaminathan, S. Methods Enzymol. 277, 590–620 (1997).

    Article  CAS  Google Scholar 

  23. Abrahams, J.P. & Leslie, A.G.W. Acta Crystallogr. D 52, 30–42 ( 1996).

    Article  CAS  Google Scholar 

  24. Jones, T.A., Zou, J.Y., Cowan, S.W. & Kjeldgaard, M.W. Acta Crystallogr. A 47, 110–119 ( 1991).

    Article  Google Scholar 

  25. Dodson, E.J., Winn, M. & Ralph, A. Methods Enzymol. 277, 620–633 (1997).

    Article  CAS  Google Scholar 

  26. Murshdov, G.N., Vagin, A.A. & Dodson, E.J. Acta Crystallogr. D 53, 240 –255 (1997).

    Article  Google Scholar 

  27. Arluison, V., Hountondji, C., Robert, B. & Grosjean, H. Biochemistry 37, 7,268–7,276 (1998).

    Article  CAS  Google Scholar 

  28. Vaguine, A.A., Richelle, J. & Wodak, S.J. Acta Crystallogr. D 55, 191 –205 (1999).

    Article  CAS  Google Scholar 

  29. Laskowski, R.A., MacArthur, M.W., Moss, D.S. & Thornton, J.M. J. Appl. Crystallogr. 26, 283–291 (1993).

    Article  CAS  Google Scholar 

  30. Esnouf, R.M. Acta Crystallogr. D 55, 938–940 (1999).

    Article  CAS  Google Scholar 

  31. Merritt, E.A. & Bacon, D.J. Meth. Enz. 277, 505–524 (1997).

    Article  CAS  Google Scholar 

  32. Nicholls, A., Sharp, K.A. & Honig, B. Proteins Struct. Funct. Genet. 11, 218–296 (1991).

    Article  Google Scholar 

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Acknowledgements

We thank R.J. Keenan and A.K. Shiau for helpful discussions during this work. Research was supported by NIH grants to J. Finer-Moore and R.M.S. and D.V.S. We also thank the SSRL and their staff for access to their beamline and help during data collection.

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Author notes

  1. Lixuan Huang

    Present address: Dupont Company, CR & D Experimental Station, P.O. Box 80402, Wilmington, Delaware, 19880, USA

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, 94143-0448, California , USA

    Paul G. Foster & Robert M. Stroud

  2. Graduate Group in Biophysics, Box 0448, University of California San Francisco, San Francisco, 94143-0448, California , USA

    Paul G. Foster & Robert M. Stroud

  3. Department of Pharmaceutical Chemistry, Box 0446, University of California San Francisco, San Francisco, California, 94143-0446, USA

    Lixuan Huang, Daniel V. Santi & Robert M. Stroud

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  1. Paul G. Foster
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Correspondence to Robert M. Stroud.

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Foster, P., Huang, L., Santi, D. et al. The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I. Nat Struct Mol Biol 7, 23–27 (2000). https://doi.org/10.1038/71219

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