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SMN Tudor domain structure and its interaction with the Sm proteins

Nature Structural Biology volume 8, pages 27–31 (2001)Cite this article

Abstract

Spinal muscular atrophy (SMA) is a common motor neuron disease that results from mutations in the Survival of Motor Neuron (SMN) gene. The SMN protein plays a crucial role in the assembly of spliceosomal uridine-rich small nuclear ribonucleoprotein (U snRNP) complexes via binding to the spliceosomal Sm core proteins. SMN contains a central Tudor domain that facilitates the SMN–Sm protein interaction. A SMA-causing point mutation (E134K) within the SMN Tudor domain prevents Sm binding. Here, we have determined the three-dimensional structure of the Tudor domain of human SMN. The structure exhibits a conserved negatively charged surface that is shown to interact with the C-terminal Arg and Gly-rich tails of Sm proteins. The E134K mutation does not disrupt the Tudor structure but affects the charge distribution within this binding site. An intriguing structural similarity between the Tudor domain and the Sm proteins suggests the presence of an additional binding interface that resembles that in hetero-oligomeric complexes of Sm proteins. Our data provide a structural basis for a molecular defect underlying SMA.

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Figure 1: Structure of the SMN Tudor domain.
Figure 2: Sm binding by the SMN Tudor domain.
Figure 3: Mapping the Sm binding site on the Tudor domain structure.
Figure 4: The Tudor domain resembles a truncated Sm fold.

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Acknowledgements

We would like to thank I. Mattaj, M. Bottomley and M. Macias for suggestions and critical reading of the manuscript. We thank J. Rappsilber for stimulating discussions at early stages of the project, and W. Bermel (Bruker, Karlsruhe) for support.

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Author notes

  1. Philipp Selenko, Remco Sprangers, Dirk Bühler and Utz Fischer: These authors contributed equally to this work.

Authors and Affiliations

  1. Structural and Computational Biology, EMBL, Meyerhofstr. 1, Heidelberg, D-69012, Germany

    Philipp Selenko, Remco Sprangers, Gunter Stier & Michael Sattler

  2. Max-Planck Institut für Biochemie, Am Klopferspitz 18a, Martinsried, D-82152, Germany

    Dirk Bühler & Utz Fischer

Authors
  1. Philipp Selenko
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  2. Remco Sprangers
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  4. Dirk Bühler
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  6. Michael Sattler
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Correspondence to Michael Sattler.

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Selenko, P., Sprangers, R., Stier, G. et al. SMN Tudor domain structure and its interaction with the Sm proteins. Nat Struct Mol Biol 8, 27–31 (2001). https://doi.org/10.1038/83014

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