Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Structural basis of BLyS receptor recognition

Nature Structural Biology volume 9, pages 288–292 (2002)Cite this article

Abstract

B lymphocyte stimulator (BLyS), a member of the tumor necrosis factor (TNF) superfamily, is a cytokine that induces B-cell proliferation and immunoglobulin secretion. We have determined the three-dimensional structure of BLyS to 2.0 Å resolution and identified receptor recognition segments using limited proteolysis coupled with mass spectrometry. Similar to other structurally determined TNF-like ligands, the BLyS monomer is a β-sandwich and oligomerizes to form a homotrimer. The receptor-binding region in BLyS is a deeper, more pronounced groove than in other cytokines. The conserved elements on the 'floor' of this groove allow for cytokine recognition of several structurally related receptors, whereas variations on the 'walls' and outer rims of the groove confer receptor specificity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Structural alignment of TNF-like cytokines.
Figure 2: BLyS structure.
Figure 3: Molecular surfaces of known TNF-family members.
Figure 4: Putative BLyS–receptor interactions.

Similar content being viewed by others

Accession codes

Accessions

Protein Data Bank

References

  1. Shu, H.B., Hu, W.H. & Johnson, H. J. Leukoc. Biol. 65, 680–683 (1999).

    Article  CAS  Google Scholar 

  2. Mukhophadhyay, A., Ni, J., Zhai, Y., Yu, G.-L. & Aggarwal, B.B. J. Biol. Chem. 274, 15978–15981 (1999).

    Article  Google Scholar 

  3. Schneider, P. et al. J. Exp. Med. 189, 1747–1756 (1999).

    Article  CAS  Google Scholar 

  4. Moore, P.A. et al. Science 285, 260–263 (1999).

    Article  CAS  Google Scholar 

  5. Mackay, F. et al. J. Exp. Med. 190, 1697–1710 (1999).

    Article  CAS  Google Scholar 

  6. Mariani, S.M., Matiba, B., Armandola, E.A. & Krammer, P.H. J. Cell Biol. 137, 221–229 (1997).

    Article  CAS  Google Scholar 

  7. Eck, M.J., Ultsch, M., Rinderknecht, E., de Vos, A.M. & Sprang, S.R. J. Biol. Chem. 267, 2119–2122 (1992).

    CAS  PubMed  Google Scholar 

  8. Eck, M.J. & Sprang, S.R. J. Biol. Chem. 264, 17595–17605 (1989).

    CAS  PubMed  Google Scholar 

  9. Hymowitz, S.G. et al. Biochemistry 39, 633–640 (2000).

    Article  CAS  Google Scholar 

  10. Cha, S.S. et al. J. Biol. Chem. 275, 31171–31177 (2000).

    Article  CAS  Google Scholar 

  11. Lam, J., Nelson, C.A., Ross, F.P., Teitelbaum, S.L. & Fremont, D.H. J. Clin. Invest. 108, 971–979 (2001).

    Article  CAS  Google Scholar 

  12. Banner, D.W. et al. Cell 73, 431–445 (1993).

    Article  CAS  Google Scholar 

  13. Kanakaraj, P. et al. Cytokine 13, 25–31 (2001).

    Article  CAS  Google Scholar 

  14. Gross, J.A. et al. Nature 404, 995–999 (2000).

    Article  CAS  Google Scholar 

  15. Marsters, S.A. et al. Curr. Biol. 10, 785–788 (2000).

    Article  CAS  Google Scholar 

  16. Wu, Y. et al. J. Biol. Chem. 275, 35478–35485 (2000).

    Article  CAS  Google Scholar 

  17. Thompson, J.S. et al. Science 293, 2108–2111 (2001).

    Article  CAS  Google Scholar 

  18. Yan, M. et al. Curr. Biol. 11, 1547–1552 (2001).

    Article  CAS  Google Scholar 

  19. Schiemann, B. et al. Science 293, 2111–2114 (2001).

    Article  CAS  Google Scholar 

  20. Singh, J. et al. Protein Sci. 7, 1124–1135 (1998).

    Article  CAS  Google Scholar 

  21. Mongkolsapaya, J. et al. Nature Struct. Biol. 6, 1048–1053 (1999).

    Article  CAS  Google Scholar 

  22. Idriss, H.T. & Naismith, J.H. Microsc. Res. Tech. 50, 184–195 (2000).

    Article  CAS  Google Scholar 

  23. Hymowitz, S.G. et al. Mol. Cell 4, 563–571 (1999).

    Article  CAS  Google Scholar 

  24. Corpet, F., Gouzy, J. & Kahn, D. Nucleic Acids Res. 26, 323–326 (1998).

    Article  CAS  Google Scholar 

  25. Rost, B. Methods Enzymol. 266, 525–539 (1996).

    Article  CAS  Google Scholar 

  26. Weinberger, S.R., Morris, T.S. & Pawlak, M. Pharmacogenomics 1, 395–416 (2000).

    Article  CAS  Google Scholar 

  27. Gross, J.A. et al. Immunity 15, 289–302 (2001).

    Article  CAS  Google Scholar 

  28. Liu, Y. et al. Cell 108, 383–394 (2002).

    Article  CAS  Google Scholar 

  29. Jancarik, J. & Kim, S.H. J. Appl. Crystallogr. 24, 409–411 (1991).

    Article  CAS  Google Scholar 

  30. Westbrook, E.M. Methods Enzymol. 114, 187–196 (1985).

    Article  CAS  Google Scholar 

  31. Otwinowski, Z. & Minor, W. In International tables for crystallography, Vol. F (eds Rossmann, M.G. & Arnold, E.) 226–235 (Kluwer Academic Publishers, Dordrecht; 2001).

    Google Scholar 

  32. Karpusas, M. et al. Structure 3, 1031–1039 (1995).

    Article  CAS  Google Scholar 

  33. Navaza, J. Acta Crystallogr. A 50, 157–163 (1994).

    Article  Google Scholar 

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

    Article  Google Scholar 

  35. Read, R.J. Acta Crystallogr. A 42, 140–149 (1986).

    Article  Google Scholar 

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

    Article  Google Scholar 

  37. Kuwata, H., Yip, T.T., Yip, C.L., Tomita, M. & Hutchens, T.W. Adv. Exp. Med. Biol. 443, 23–32 (1998).

    Article  CAS  Google Scholar 

  38. Guex, N. & Peitsch, M.C. Electrophoresis 18, 2714–2723 (1997).

    Article  CAS  Google Scholar 

  39. Carson, M. J. Appl. Crystallogr. 24, 958–961 (1991).

    Article  Google Scholar 

  40. Nicholls, A., Sharp, K. & Honig, B. Proteins Struct. Funct. Genet. 11, 281–296 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank M. Zhang for her contribution in purifying BLyS protein, T. Kwong for excellent work preparing mass spectrometry experiments, other Arnold lab members and the staff at the Cornell High Energy Synchrotron Source and BioCARS at the Advanced Photon Source for assistance, C. Rosen for valuable discussions and enthusiastic support of the collaboration and the Arnold lab gratefully acknowledges HGS for financial support.

Author information

Authors and Affiliations

  1. Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University, 679 Hoes Lane, Piscataway, 08816, New Jersey, USA

    Deena A. Oren, Yulia Volovik, Chhaya Dharia, Kalyan Das & Eddy Arnold

  2. Department of Protein Development, Human Genome Sciences, 9410 Key West Avenue, Rockville, 20850, Maryland, USA

    Yuling Li, Tina S. Morris, Olga Galperina & Reiner Gentz

Authors
  1. Deena A. Oren
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yulia Volovik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tina S. Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chhaya Dharia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kalyan Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Olga Galperina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Reiner Gentz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eddy Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eddy Arnold.

Ethics declarations

Competing interests

The Arnold laboratory received funds from HGS to support some of the studies reported here. D.A.O. and E.A. were paid consultants to Human Genome Sciences, Inc., during part of the period during which this work was done. Y.L., O.G. and R.G. are employees of Human Genome Sciences, Inc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oren, D., Li, Y., Volovik, Y. et al. Structural basis of BLyS receptor recognition. Nat Struct Mol Biol 9, 288–292 (2002). https://doi.org/10.1038/nsb769

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsb769

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing