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Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization

Nature Structural Biology volume 7, pages 871–875 (2000)Cite this article

Abstract

The crystal structure of the core domain (N-terminal 30 kDa domain) of cytoskeletal protein 4.1R has been determined and shows a cloverleaf-like architecture. Each lobe of the cloverleaf contains a specific binding site for either band 3, glycophorin C/D or p55. At a central region of the molecule near where the three lobes are joined are two separate calmodulin (CaM) binding regions. One of these is composed primarily of an α-helix and is Ca2+ insensitive; the other takes the form of an extended structure and its binding with CaM is dramatically enhanced by the presence of Ca2+, resulting in the weakening of protein 4.1R binding to its target proteins. This novel architecture, in which the three lobes bind with three membrane associated proteins, and the location of calmodulin binding sites provide insight into how the protein 4.1R core domain interacts with membrane proteins and dynamically regulates cell shape in response to changes in intracellular Ca2+ levels.

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Figure 1: Ribbon diagram, surface and density maps, and amino acid sequence of the protein 4.1R core domain.
Figure 2: Space filling representation and stereo view of the protein 4.1R core domain showing the binding regions for band 3, glycophorin C/D, p55 and CaM.
Figure 3: Space filling representations of CaM binding regions.
Figure 4: Schematic model of CaM regulation of the protein 4.1R core domain.

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References

  1. Conboy, J.G. Semin. Hematol. 30, 58–73 (1993).

    CAS  PubMed  Google Scholar 

  2. Parra, M., et al. J. Biol. Chem. 275, 3247– 3255 (2000).

    Article  CAS  Google Scholar 

  3. Marfatia, S.M., Lue, R.A., Branton, D. & Chishti, A. H. J. Biol. Chem. 270, 715–719 ( 1995).

    Article  CAS  Google Scholar 

  4. Nunomura, W., Takakuwa, Y., Parra, M., Conboy, J. & Mohandas, N. J. Biol. Chem. 275, 24540– 24546 (2000).

    Article  CAS  Google Scholar 

  5. Pasternack, G.R., Anderson, R.A., Leto, T.L. & Marchesi, V.T. J. Biol. Chem. 260, 3676–3683 (1985).

    CAS  PubMed  Google Scholar 

  6. Gould, K.L., Bretscher, A., Esch, F.S. & Hunter, T. EMBO J. 8, 4133–4142 ( 1989).

    Article  CAS  Google Scholar 

  7. Takakuwa, Y. & Mohandas, N. J. Clin. Invest. 82 , 394–400 (1988).

    Article  CAS  Google Scholar 

  8. Ikura, M., Clore, G.M., Gronenborn, A.M., Zhu, G., Klee, C.B. & Bax, A. Science 256, 632–638 ( 1992).

    Article  CAS  Google Scholar 

  9. Meador, W.E., Means, A.R. & Quiocho, F.A. Science 257, 1251– 1255 (1992).

    Article  CAS  Google Scholar 

  10. Meador, W.E., Means, A.R. & Quiocho, F.A. Science 262, 1718– 1721 (1993).

    Article  CAS  Google Scholar 

  11. Osawa, M., et al. Nature Struct. Biol. 6, 819– 824 (1999).

    Article  CAS  Google Scholar 

  12. Dasgupta, M., Honeycutt, T. & Blumenthal, D.K. J. Biol. Chem. 264, 17156– 17163 (1989).

    CAS  PubMed  Google Scholar 

  13. Zhou, N., Yuan, T., Mak, A.S. & Vogel, H.J. Biochemistry 36, 2817–2825 (1997).

    Article  CAS  Google Scholar 

  14. Goldberg, J., Nairn, A.C. & Kuriyan, J. Cell 84, 875– 887 (1996).

    Article  CAS  Google Scholar 

  15. Nunomura, W., Takakuwa, Y., Parra, M., Conboy, J.G. & Mohandas, N. J. Biol. Chem. 275, 6360– 6367 (2000).

    Article  CAS  Google Scholar 

  16. Jöns, T. & Drenckhahn, D. EMBO J. 11, 2863–2867 (1992).

    Article  Google Scholar 

  17. Han, B.-G., Nunomura, W., Wu, H., Mohandas, N. & Jap, B.K. Acta Crystallogr. D 56, 187– 188 (2000).

    Article  CAS  Google Scholar 

  18. Hendrickson, W.A., Horton, J.R. & LeMaster, D.M. EMBO J. 9, 1665– 1672 (1990).

    Article  CAS  Google Scholar 

  19. Otwinoski Z. & Minor, W. Methods Enzymol. 276, 307–326 (1997).

    Article  Google Scholar 

  20. Terwilliger, T. C. Acta Crystallogr. D 50, 17–23 (1994).

    Article  CAS  Google Scholar 

  21. Collaborative Computational Project, Number 4. Acta Crystallogr. D 50, 760–763 (1994).

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

    Article  Google Scholar 

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

    Article  Google Scholar 

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Acknowledgements

This work was supported by the Director, Office of Science, Office of Biological and Environment Research, Life Sciences Division, of the U.S. Department of Energy (DOE), by National Institutes of Health (NIH) Research grants and by the Ministry of Education of Japan. We also thank the staff at the ALS beam line 5.0.2 and the NSLS beam line X25 for their assistance during data collection. The synchrotron facilities are supported by DOE (ALS and NSLS) and NIH (NSLS). We are thankful to P.J. Walian for helpful discussions and critical reading of the manuscript.

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Authors and Affiliations

  1. Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, 94720, California, USA

    Bong-Gyoon Han, Narla Mohandas & Bing K. Jap

  2. Department of Biochemistry, Tokyo Women's Medical University, Tokyo, 162-8666, Japan

    Wataru Nunomura & Yuichi Takakuwa

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  1. Bong-Gyoon Han
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  2. Wataru Nunomura
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  4. Narla Mohandas
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Correspondence to Narla Mohandas or Bing K. Jap.

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Han, BG., Nunomura, W., Takakuwa, Y. et al. Protein 4.1R core domain structure and insights into regulation of cytoskeletal organization. Nat Struct Mol Biol 7, 871–875 (2000). https://doi.org/10.1038/82819

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