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Solution structures of the two PBZ domains from human APLF and their interaction with poly(ADP-ribose)

Nature Structural & Molecular Biology volume 17, pages 241243 (2010) | Download Citation

Abstract

Addition of poly(ADP-ribose) (PAR) is an important post-translational modification in higher eukaryotes. Several DNA repair and checkpoint proteins possess specific PAR-binding zinc-finger (PBZ) modules critical for function. Here, we present solution structures of the two PBZ modules of aprataxin and PNK–like factor (APLF), revealing a novel type of zinc finger. By combining in vivo PAR-binding data with NMR interaction data using PAR fragments, we propose a structural basis for PBZ-PAR recognition.

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References

  1. 1.

    , , & Biochem. J. 342, 249–268 (1999).

  2. 2.

    , & Genes Dev. 19, 1951–1967 (2005).

  3. 3.

    , , & Nat. Rev. Mol. Cell Biol. 7, 517–528 (2006).

  4. 4.

    et al. EMBO J. 24, 1911–1920 (2005).

  5. 5.

    et al. Science 325, 1240–1243 (2009).

  6. 6.

    et al. Nat. Struct. Mol. Biol. 16, 923–929 (2009).

  7. 7.

    , , & J. Biol. Chem. 275, 40974–40980 (2000).

  8. 8.

    et al. Nature 451, 81–85 (2008).

  9. 9.

    , , & Mol. Cell. Biol. 27, 3793–3803 (2007).

  10. 10.

    & Nature 406, 430–435 (2000).

  11. 11.

    , , & Tetrahedron 64, 2871–2876 (2008).

  12. 12.

    , , & Nat. Struct. Mol. Biol. 11, 257–264 (2004).

  13. 13.

    & Nat. Struct. Mol. Biol. 15, 1343–1351 (2008).

  14. 14.

    , , , & DNA Repair (Amst.) 7, 292–302 (2008).

  15. 15.

    , , , & Mol. Cell. Biol. 28, 4620–4628 (2008).

Download references

Acknowledgements

We thank A. Murzin, A. Andreeva and C. Rademacher for helpful discussions, G. Smith (AstraZeneca) for the PARP inhibitor KU-0058948, W. Vranken for help with data deposition and C. Oubridge for help with MS. S.E. was funded by a studentship from Boehringer Ingelheim Fonds, C.B. by a fellowship from the Federation of European Biochemical Societies and I.A. by fellowships from Cancer Research UK and the Louis-Jeantet Foundation.

Author information

Author notes

    • Sebastian Eustermann
    •  & Christoph Brockmann

    These authors contributed equally to this work.

Affiliations

  1. MRC Laboratory of Molecular Biology, Cambridge, UK.

    • Sebastian Eustermann
    • , Christoph Brockmann
    • , Ji-Chun Yang
    • , David Loakes
    •  & David Neuhaus
  2. Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.

    • Pawan Vinod Mehrotra
    •  & Ivan Ahel
  3. Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Hertfordshire, UK.

    • Stephen C West

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Contributions

S.E. cloned the construct; S.E., P.V.M. and I.A. designed and performed biochemical experiments; D.L. synthesized the RFA ligand; P.V.M. performed the in vivo binding analyses; S.E., J.-C.Y. and C.B. performed and analyzed NMR experiments; S.E., C.B. and D.N. calculated and analyzed the structures; S.E., I.A., S.C.W. and D.N. wrote the manuscript; D.N. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David Neuhaus.

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    Supplementary Text and Figures

    Supplementary Methods, Supplementary Figures 1–11 and Supplementary Tables 1 and 2

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DOI

https://doi.org/10.1038/nsmb.1747