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Structural basis of cell–cell adhesion by NCAM

Nature Structural Biology volume 7, pages 389–393 (2000)Cite this article

Abstract

The neural cell adhesion molecule NCAM, a member of the immunoglobulin superfamily, mediates cell–cell recognition and adhesion via a homophilic interaction. NCAM plays a key role during development and regeneration of the nervous system and is involved in synaptic plasticity associated with memory and learning. The 1.85 Å crystal structure of the two N-terminal extracellular domains of NCAM reported here provides a structural basis for the homophilic interaction. The molecular packing of the two-domain structure reveals a cross shaped antiparallel dimer, and provides fundamental insight into trans-cellular recognition mediated by NCAM.

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Figure 1: NCAM IgI-IgII structure and homophilic binding.
Figure 2: The homophilic binding interface of NCAM.
Figure 3: Sequence alignment of NCAM IgI-IgII dimers from several species.

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References

  1. Rønn, L.C.B., Hartz, B.P. & Bock, E. Exp. Gerontol. 33, 853–864 (1998).

    Article  Google Scholar 

  2. Hall, H., Walsh, F.S. & Doherty, P. Cell Adhes. Commun. 3, 441–450 (1996).

    Article  CAS  Google Scholar 

  3. Hoffman, K.B. Cell. Mol. Neurobiol. 18, 461–475 (1998).

    Article  CAS  Google Scholar 

  4. Arami, S., Jucker, M., Schachner, M. & Welzl, H. Behav. Brain Res. 81, 81–87 (1996).

    Article  CAS  Google Scholar 

  5. Skibo, G.G., Davies, H.A., Rusakov, D.A., Stewart, M.G. & Schachner, M. Neuroscience 82, 1–5 (1998).

    Article  CAS  Google Scholar 

  6. Cremer, H. et al. Nature 367, 455–459 (1994).

    Article  CAS  Google Scholar 

  7. Maidment, S.L., Rucklidge, G.J., Rooprai, H.K. & Pilkington, G.J. Cancer Lett. 116, 71–77 (1997).

    Article  CAS  Google Scholar 

  8. Luo, J., Lubaroff, D.M. & Hendrix, M.J.C. Cancer Res. 59, 3552–3556 (1999).

    CAS  PubMed  Google Scholar 

  9. Andersson, A.-M. et al. Biochem. J. 290, 641–648 (1993).

    Article  CAS  Google Scholar 

  10. Gaardsvoll, H. et al. Eur. J. Cell Biol. 61, 100–107 (1993).

    CAS  PubMed  Google Scholar 

  11. Møller, C.J., Byskov, A.G., Roth, J., Celis, J.E. & Bock, E. Anat. Embryol. 184, 541–548 (1991).

    Article  Google Scholar 

  12. Bloch, R.J. J. Cell Biol. 116, 449–463 (1992).

    Article  CAS  Google Scholar 

  13. Jacobson, K.A . et al. Biochim. Biophys. Acta 1330, 138–144 (1997).

    Article  CAS  Google Scholar 

  14. Gegelashvili, G. & Bock, E., Treatise Biomembranes 3, 33–75 (1996).

    Article  CAS  Google Scholar 

  15. Kasper, C. et al. J. Neurosci. Res. 46, 173–186 (1996).

    Article  CAS  Google Scholar 

  16. Lahrtz, F., Horstkorte, R., Cremer, H., Schachner, M. & Montag, D. J. Neurosci. Res. 50, 62–68 (1997).

    Article  CAS  Google Scholar 

  17. Kiss, J.Z. & Rougon, G. Curr. Opin. Neurobiol. 7, 640–646 (1997).

    Article  CAS  Google Scholar 

  18. Cunningham, B.A. et al. Science 236, 799–806 (1987).

    Article  CAS  Google Scholar 

  19. Hall, B.A. & Rutishauser, U. J. Cell Biol. 104,1579–1586 (1987).

    Google Scholar 

  20. Sandig, M., Rao, Y., Kalnins, V.I. & Siu, C.-H. Biochem. Cell Biol. 74, 373–381 (1996).

    Article  CAS  Google Scholar 

  21. Zhou, H., Fuks, A., Alcaraz, G., Bolling, T.J. & Stanners, C.P. J. Cell Biol. 122, 951–960 (1993).

    Article  CAS  Google Scholar 

  22. Ranheim, T.S., Edelman, G.M. & Cunningham, B.A. Proc. Natl. Acad. Sci. USA 93, 4071–4075 (1996).

    Article  CAS  Google Scholar 

  23. Frei, T., von Bohlen und Halbach, F., Wille, W. & Schachner, M. J. Cell Biol. 118, 177–194 (1992).

    Article  CAS  Google Scholar 

  24. Kiselyov, V.V. et al. J. Biol. Chem. 272, 10125–10134 (1997).

    Article  CAS  Google Scholar 

  25. Thomsen, N.K. et al. Nature Struct. Biol. 3, 581–585 (1996).

    Article  CAS  Google Scholar 

  26. Jensen, P.H. et al. Nature Struct. Biol. 6, 486–493 (1999).

    Article  CAS  Google Scholar 

  27. Atkins, A.R. et al. FEBS Lett. 451, 162–168 (1999).

    Article  CAS  Google Scholar 

  28. Chothia C. & Jones, E.Y. Annu. Rev. Biochem. 66, 823–862 (1997).

    Article  CAS  Google Scholar 

  29. Su, X.-D. et al. Science 281, 991–995 (1999).

    Article  Google Scholar 

  30. Conte, L.L., Chothia, C. & Janin, J. J. Mol. Biol. 285, 2177–2198 (1999).

    Article  Google Scholar 

  31. Reyes, A.A., Akeson, R., Brezina, L. & Cole, G. Cell Regul. 1, 567–576 (1990).

    Article  CAS  Google Scholar 

  32. Kallapur S.G. & Akeson, R.A. J. Neurosci. Res. 33, 538–548 (1992).

    Article  CAS  Google Scholar 

  33. Paoloni-Giacobino, A., Chen, H. & Antonarakis, S.E. Genomics 43, 43–51 (1997).

    Article  CAS  Google Scholar 

  34. Holm, L. & Sander, C. J. Mol. Biol. 233, 123–138 (1993).

    Article  CAS  Google Scholar 

  35. Koch, A.W., Bozic, D., Pertz, O. & Engel, J. Curr. Opin. Struct. Biol. 9, 275–281 (1999).

    Article  CAS  Google Scholar 

  36. Kasper, C., Rasmussen, H., Berezin, V., Bock, E. & Larsen, I.K. Acta Crystallogr. D 55, 1598–1600 (1999).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  38. Terwilliger, T.C. & Berendzen, J. Acta Crystallogr. D 55, 849–861 (1999).

    Article  CAS  Google Scholar 

  39. de la Fortelle, E. & Bricogne, G. Methods Enzymol. 276, 472–494 (1997).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  41. Brünger, A.T. Acta Crystallogr. D 54, 905–921 (1998).

    Article  Google Scholar 

  42. Kleywegt, G.J. & Jones, T.A. Structure 4, 1395–1400 (1996).

    Article  CAS  Google Scholar 

  43. Bork, P., Downing, A.K., Kieffer, B. & Campbell, I. Q. Rev. Biophys. 29, 119–167 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Access to the synchrotron source at ESRF (BM14) is deeply appreciated. G. Lennart and A. Thompson are thanked for expert technical assistance during data collection, D. I. Stuart, University of Oxford, for map averaging in GAP, and V. Soroka, University of Copenhagen, for assistance during protein expression. This work was supported by NeuroScience PharmaBiotec, The Lundbeck Foundation, The Danish Biotechnology Programme, and The Dansync Center for Synchrotron Radiation. We thank the European Union for support of the work at the EMBL Hamburg through the TMR/LSF programme.

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Author notes

  1. Hanne Rasmussen

    Present address: Novo Nordisk A/S, Novo Allé, DK-2880, Bagsværd, Denmark

Authors and Affiliations

  1. Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark

    Christina Kasper, Hanne Rasmussen, Jette S. Kastrup & Ingrid K. Larsen

  2. Laboratory of Molecular Biophysics, Oxford Centre for Molecular Sciences, South Parks Road, Oxford, OX1 3QU, England

    Shinji Ikemizu & E. Yvonne Jones

  3. Protein Laboratory, Institute of Molecular Pathology, Panum Institute, University of Copenhagen, Copenhagen N, DK-2200, Denmark

    Vladimir Berezin & Elisabeth Bock

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Correspondence to Ingrid K. Larsen.

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Kasper, C., Rasmussen, H., Kastrup, J. et al. Structural basis of cell–cell adhesion by NCAM. Nat Struct Mol Biol 7, 389–393 (2000). https://doi.org/10.1038/75165

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