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Dimeric structure of the Oxytricha nova telomere end-binding protein α-subunit bound to ssDNA

Nature Structural Biology volume 9, pages 182–187 (2002)Cite this article

Abstract

Telomeres are the specialized protein–DNA complexes that cap and protect the ends of linear eukaryotic chromosomes. The extreme 3′ end of the telomeric DNA in Oxytricha nova is bound by a two-subunit sequence-specific and 3′ end-specific protein called the telomere end-binding protein (OnTEBP). Here we describe the crystal structure of the α-subunit of OnTEBP in complex with T4G4 single-stranded telomeric DNA. This structure shows an (α–ssDNA)2 homodimer with a large ∼7,000 Å2 protein–protein interface in which the domains of α are rearranged extensively from their positions in the structure of an α–β–ssDNA ternary complex. The (α–ssDNA)2 complex can bind two telomeres on opposite sides of the dimer and, thus, acts as a protein mediator of telomere–telomere associations. The structures of the (α–ssDNA)2 dimer presented here and the previously described α–β–ssDNA complex demonstrate that OnTEBP forms multiple telomeric complexes that potentially mediate the assembly and disassembly of higher order telomeric structures.

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Figure 1: Structures of O. nova telomere end-binding protein complexes.
Figure 2: ssDNA register shift and protein–protein interactions inter-relating the two OnTEBP complexes.
Figure 3: Stereo image of the protein–ssDNA interactions in the (α–ssDNA)2 dimer and structural alignment of Pot1 sequence homology.
Figure 4: OnTEBP α-subunit as a mediator of higher order telomere–telomere association.

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References

  1. Blackburn, E.H. Cell 106, 661–673 (2001).

    Article  CAS  Google Scholar 

  2. Cooper, J.P. Curr. Opin. Genet. Dev. 10, 169–177 (2000).

    Article  CAS  Google Scholar 

  3. Price, C.M. Curr. Opin. Genet. Dev. 9, 218–224 (1999).

    Article  CAS  Google Scholar 

  4. Rabl, C. Morphologisches Jarhbruch 10, 214–330 (1885).

    Google Scholar 

  5. Comings, D.E. Hum. Genet. 53, 131–143 (1980).

    Article  CAS  Google Scholar 

  6. Dandjinou, A.T. et al. Histol. Histopathol. 14, 517–524 (1999).

    CAS  PubMed  Google Scholar 

  7. Blackburn, E.H. & Gall, J.G. J. Mol. Biol. 120, 33–53 (1978).

    Article  CAS  Google Scholar 

  8. Klobutcher, L.A., Swanton, M.T., Donini, P. & Prescott, D.M. Proc. Natl. Acad. Sci. USA 78, 3015–3019 (1981).

    Article  CAS  Google Scholar 

  9. Lipps, H.J., Gruissem, W. & Prescott, D.M. Proc. Natl. Acad. Sci. USA 79, 2495–2499 (1982).

    Article  CAS  Google Scholar 

  10. Gottschling, D.E. & Zakian, V.A. Cell 47, 195–205 (1986).

    Article  CAS  Google Scholar 

  11. Lingner, J. & Cech, T.R. Proc. Natl. Acad. Sci. USA 93, 10712–10717 (1996).

    Article  CAS  Google Scholar 

  12. Price, C.M. & Cech, T.R. Genes Dev. 1, 783–793 (1987).

    Article  CAS  Google Scholar 

  13. Price, C.M. Mol. Cell. Biol. 10, 3421–3431 (1990).

    Article  CAS  Google Scholar 

  14. Fang, G.W. & Cech, T.R. Nucleic Acids Res. 19, 5515–5518 (1991).

    Article  CAS  Google Scholar 

  15. Baumann, P. & Cech, T.R. Science 292, 1171–1175 (2001).

    Article  CAS  Google Scholar 

  16. Gray, J.T., Celander, D.W., Price, C.M. & Cech, T.R. Cell 67, 807–814 (1991).

    Article  CAS  Google Scholar 

  17. Fang, G. & Cech, T.R. Proc. Natl. Acad. Sci. USA 90, 6056–6060 (1993).

    Article  CAS  Google Scholar 

  18. Horvath, M.P., Schweiker, V.L., Bevilacqua, J.M., Ruggles, J.A. & Schultz, S.C. Cell 95, 963–974 (1998).

    Article  CAS  Google Scholar 

  19. Fang, G., Gray, J.T. & Cech, T.R. Genes Dev. 7, 870–882 (1993).

    Article  CAS  Google Scholar 

  20. Price, C.M. & Cech, T.R. Biochemistry 28, 769–774 (1989).

    Article  CAS  Google Scholar 

  21. Prescott, D.M. Microbiol. Rev. 58, 233–267 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Raghuraman, M.K. & Cech, T.R. Cell 59, 719–728 (1989).

    Article  CAS  Google Scholar 

  23. Raghuraman, M.K., Dunn, C.J., Hicke, B.J. & Cech, T.R. Nucleic Acids Res. 17, 4235–4253 (1989).

    Article  CAS  Google Scholar 

  24. Froelich-Ammon, S.J., Dickinson, B.A., Bevilacqua, J.M., Schultz, S.C. & Cech, T.R. Genes Dev. 12, 1504–1514 (1998).

    Article  CAS  Google Scholar 

  25. Murzin, A.G. EMBO J. 12, 861–867 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Hicke, B.J., Willis, M.C., Koch, T.H. & Cech, T.R. Biochemistry 33, 3364–3373 (1994).

    Article  CAS  Google Scholar 

  28. Saenger, W. Principles of nucleic acid structure (Springer-Verlag, New York; 1984).

    Book  Google Scholar 

  29. Murti, K.G. & Prescott, D.M. Chromosome Res. In the press (2002).

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

    Article  CAS  Google Scholar 

  31. Brünger, A.T. X-PLOR Version 3.1 (Yale University Press, New Haven; 1992)

    Google Scholar 

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

    Article  Google Scholar 

  33. Brünger, A.T. et al. Acta Crystallogr. D 54, 905–921 (1998).

    Article  Google Scholar 

  34. Esnouf, R.M.I. Acta Crystallogr. D 55, 938–940 (1997).

    Article  Google Scholar 

  35. Nicholls, A. Sharp, K.A. & Honig, B. Proteins 11, 281–296 (1991)

    Article  CAS  Google Scholar 

  36. Swanton, M.T., Heumann, J.M. & Prescott, D.M. Chromosoma 77, 217–227 (1980).

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank D.M. Prescott for discussions pertaining to O. nova gene organization and providing us with O. nova macronuclei; D. Lyons and T.R. Cech for antibodies; M.P. Horvath, D.S. Classen, D.L. Theobald, and J.M. Bevilacqua for their support and advice during the course of this project; and A.V. Johnson for assistance with the macronuclear lysis experiments. This work was supported by grants from the American Cancer Society and National Institutes of Health.

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Author notes

  1. Olve B. Peersen

    Present address: Department of Biochemistry & Molecular Biology, Colorado State University, Fort Collins, Colorado, 80523-1870, USA

  2. James A. Ruggles

    Present address: Amylin Pharmaceuticals Inc., 9373 Towne Centre Drive, San Diego, California, 92121, USA

  3. Steve C. Schultz

    Present address: Math/Science Division, Diné College, Tsaile, Navajo Nation, Arizona, 86556, USA

Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Colorado, Boulder, 80309-0215, Colorado, USA

    Olve B. Peersen, James A. Ruggles & Steve C. Schultz

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  1. Olve B. Peersen
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Correspondence to Olve B. Peersen.

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Peersen, O., Ruggles, J. & Schultz, S. Dimeric structure of the Oxytricha nova telomere end-binding protein α-subunit bound to ssDNA. Nat Struct Mol Biol 9, 182–187 (2002). https://doi.org/10.1038/nsb761

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