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Comparative analysis of carbohydrate binding properties of Sambucus nigra lectins and ribosome-inactivating proteins

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Abstract

In the past three decades a lot of research has been done on the extended family of carbohydrate-binding proteins from Sambucus nigra, including several so-called type 2 RIPs as well as hololectins. Although all these proteins have been studied for their carbohydrate-binding properties using hapten inhibition assays, detailed carbohydrate specificity studies have only been performed for a few Sambucus proteins. In particular SNA-I, has been studied extensively. Because of its unique binding characteristics this lectin was developed as an important tool in glycoconjugate research to detect sialic acid containing glycoconjugates. At present much less information is available with respect to the detailed carbohydrate binding specificity of other S. nigra lectins and RIPs, and as a consequence their applications remain limited. In this paper we report a comparative analysis of several lectins from S. nigra using the glycan microarray technology. Ultimately a better understanding of the ligands for each lectin can contribute to new/more applications for these lectins in glycoconjugate research. Furthermore, the data from glycan microarray analyses combined with the previously obtained sequence information can help to explain how evolution within a single lectin family eventually yielded a set of carbohydrate-binding proteins with a very broad specificity range.

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References

  1. Broekaert, W.F., Nsimba-Lubaki, M., Peeters, B., Peumans, W.J.: A lectin from elder (Sambucus nigra L.) bark. Biochem. J. 221, 163–169 (1984)

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Shibuya, N., Goldstein, I.J., Broekaert, W.F., Nsimba-Lubaki, M., Peeters, B., Peumans, W.J.: The elderberry (Sambucus nigra L.) bark lectin recognizes the NeuAc(α2,6)-Gal/GalNAc sequence. J. Biol. Chem. 262, 1596–1601 (1987)

    CAS  PubMed  Google Scholar 

  3. Van Damme, E.J.M., Barre, A., Rougé, P., Van Leuven, F., Peumans, W.J.: The NeuAc(a-2,6) Gal/Gal-NAc-binding lectin from elderberry (Sambucus nigra) bark, a type-2 ribosome-inactivating protein with an unusual specificity and structure. Eur. J. Biochem. 235, 128–137 (1996)

    Article  PubMed  Google Scholar 

  4. Girbés, T., Ferreras, J.M., Arias, F.J., Muñoz, R., Iglesias, R., Jimenez, P., Rojo, M.A., Arias, Y., Perez, Y., Benitez, J., Sanchez, D., Gayoso, M.J.: Non-toxic type 2 ribosome-inactivating proteins (RIPs) from Sambucus: occurrence, cellular and molecular activities and potential uses. Cell. Mol. Biol. 49, 537–545 (2003)

    PubMed  Google Scholar 

  5. Peumans, W.J., Kellens, J.T.C., Allen, A.K., Van Damme, E.J.M.: Isolation and characterization of a seed lectin from elderberry (Sambucus nigra) and its relationship to the bark lectins. Carbohydr. Res. 213, 7–17 (1991)

    Article  CAS  PubMed  Google Scholar 

  6. Kaku, H., Peumans, W.J., Goldstein, I.J.: Isolation and characterization of a second lectin (SNA-II) present in elderberry (Sambucus nigra L.) bark. Arch. Biochem. Biophys. 277, 255–262 (1990)

    Article  CAS  PubMed  Google Scholar 

  7. Mach, L., Waltraud, S., Ammann, M., Poetsch, J., Bertsch, W., Marz, L., Glossl, J.: Purification and partial characterization of a novel lectin from elder (Sambucus nigra L.) fruit. Biochem. J. 278, 667–671 (1991)

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Van Damme, E.J.M., Barre, A., Rougé, P., Leuven, F.V., Peumans, W.J.: Characterization and molecular cloning of Sambucus nigra agglutinin V (nigrin b), a GalNAc-specific type-2 ribosome-inactivating protein from the bark of elderberry (Sambucus nigra). Eur. J. Biochem. 237, 505–513 (1996)

    Article  PubMed  Google Scholar 

  9. Van Damme, E.J.M., Roy, S., Rarre, A., Rougé, P., Van Leuven, F., Peumans, W.J.: The major elderberry fruit protein is a lectin derived from a truncated type 2 ribosome-inactivating protein. Plant J. 12, 1251–1260 (1997)

    Article  PubMed  Google Scholar 

  10. Peumans, W.J., Roy, S., Barre, A., Rougé, P., Van Leuven, F., Van Damme, E.J.: Elderberry (Sambucus nigra) contains truncated Neu5Ac(α-2,6)Gal/GalNAc-binding type 2 ribosome-inactivating proteins. FEBS Lett. 425, 35–39 (1998)

    Article  CAS  PubMed  Google Scholar 

  11. Van Damme, E.J.M., Barre, A., Rougé, P., Van Leuven, F., Peumans, W.J.: Isolation and molecular cloning of a novel type 2 ribosome-inactivating protein with an inactive B-chain from elderberry (Sambucus nigra) bark. J. Biol. Chem. 272, 8353–8360 (1997)

    Article  PubMed  Google Scholar 

  12. Mach, L., Kerschbaumer, R., Schwihla, H., Glossl, J.: Elder (Sambucus nigra L.) fruit lectin (SNA-IV) occurs in monomeric, dimeric and oligomeric isoforms. Biochem. J. 315, 1061 (1996)

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Shibuya, N., Tazaki, K., Song, Z.W., Tarr, G.E., Goldstein, I.J., Peumans, W.J.: A comparative study of bark lectins from three elderberry (Sambucus) species. J. Biochem. 106, 1098–1103 (1989)

    CAS  PubMed  Google Scholar 

  14. Maveyraud, L., Niwa, H., Guillet, V., Svergun, D.I., Konarev, P.V., Palmer, R.A., Peumans, W.J., Rouge, P., Van Damme, E.J.M., Reynolds, C.D., Mourey, L.: Structural basis for sugar recognition, including the Tn carcinoma antigen, by the lectin SNA-II from Sambucus nigra. Proteins 75, 89–103 (2009)

    Article  CAS  PubMed  Google Scholar 

  15. Rhodes, J.M., Campbell, B.J., Yu, L.G.: Lectin-epithelial interactions in the human colon. Biochem. Soc. Trans. 36, 1482–1486 (2008)

    Article  CAS  PubMed  Google Scholar 

  16. Boscher, C., Dennis, J.W., Nabi, I.R.: Glycosylation, galectins and cellular signaling. Curr. Opin. Cell Biol. 23, 383–392 (2011)

    Article  CAS  PubMed  Google Scholar 

  17. Van Damme, E.J.M., Smith, D.F., Cummings, R., Peumans, W.J.: Glycan arrays to decipher the specificity of plant lectins. Adv. Exp. Med. Biol. 705, 757–768 (2011)

    Article  PubMed  Google Scholar 

  18. Blixt, O., Head, S., Mondala, T., Scanlan, C., Huflejt, M.E., Alvarez, R., Bryan, M.C., Fazio, F., Calarese, D., Stevens, J., Razi, N., Stevens, D.J., Skehel, J.J., Van Die, I., Burton, D.R., Wilson, I.A., Cummings, R., Bovin, N., Wong, C.H., Paulson, J.C.: Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc. Natl. Acad. Sci. U. S. A. 101, 17033–17038 (2004)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Thompson, J.D., Higgins, D.G., Gilson, T.J.: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Papadopoulos, J.S., Agarwala, R.: COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics 23, 1073–1079 (2007)

    Article  CAS  PubMed  Google Scholar 

  21. Smith, D.F., Song, X., Cummings, R.D.: Use of glycan microarrays to explore specificity of glycan-binding proteins. Methods Enzymol. 480, 417–444 (2010)

    Article  CAS  PubMed  Google Scholar 

  22. Song, X., Yu, H., Chen, X., Lasanajak, Y., Tappert, M.M., Air, G.M., Tiwari, V.K., Cao, H., Chokhawala, H.A., Zheng, H., Cummings, R.D., Smith, D.F.: A sialylated glycan microarray reveals novel interactions of modified sialic acids with proteins and viruses. J. Biol. Chem. 286, 31610–31622 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Padler-Karavani, V., Song, X., Yu, H., Hurtado-Ziola, H., Huang, S., Muthana, S., Chokhawala, H.A., Cheng, J., Verhagen, A., Langereis, M.A., Kleene, R., Schachner, M., De Groot, R.J., Lasanajak, Y., Matsuda, H., Schwab, R., Chen, X., Smith, D.F., Cummings, R.D., Varki, A.: Cross-comparison of protein recognition of sialic acid diversity on two novel sialoglycan microarrays. J. Biol. Chem. 287, 22593–22608 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Stanley, P., Cummings, R.D.: Structures common to different glycans. In: Varki, A., Cummings, R.D., Esko, J.D., Freeze, P., Stanley, P., Bertozzi, C.R., Hart, G.W., Etzler, M.E. (eds.) Essentials of Glycobiology, 2nd edn, pp. 175–198. Cold Spring Harbor Laboratory Press, NY (2009)

    Google Scholar 

  25. Hazes, B.: The (QxW)3 domain: A flexible lectin scaffold. Protein Sci. 5, 1490–1501 (1996)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Robertus, J.D., Ready, M.P.: Ricin B-chain and discoidin I share a common primitive protein fold. J. Biol. Chem. 259, 13953–13956 (1984)

    CAS  PubMed  Google Scholar 

  27. Rutenber, E., Ready, M., Robertus, J.: Structure and evolution of ricin B-chain. Nature 326, 624–626 (1987)

    Article  CAS  PubMed  Google Scholar 

  28. Montfort, W., Villafranca, J.E., Monzingo, A.F., Ernst, S.R., Katzin, B., Rutenber, E., Xuong, N.H., Hamlin, R., Robertus, J.D.: The three-dimensional structure of ricin at 2.8 Å. J. Biol. Chem. 262, 5398–5403 (1987)

    CAS  PubMed  Google Scholar 

  29. Rutenber, E., Roberus, J.D.: Structure of ricin B-chain at 2.5 Å resolution. Proteins 10, 240–250 (1991)

    Article  CAS  PubMed  Google Scholar 

  30. Pascal, J.M., Day, P.J., Monzingo, A.F., Ernst, S.R., Robertus, J.D., Iglesias, R., Pérez, Y., Férreras, J.M., Citores, L., Girbés, T.: 2.8-Å Crystal structure of a nontoxic type-II ribosome-inactivating protein, ebulin l. proteins: structure, function. Genetics 43, 319–326 (2001)

    CAS  Google Scholar 

  31. Kaku, H., Kaneko, H., Minamihara, N., Iwata, K., Jordan, E.T., Rojo, M.A., Minami-Ishii, N., Minami, E., Hisajima, S., Shibuya, N.: Elderberry bark lectins evolved to recognize Neu5Acα2,6Gal/GalNAc sequence from a Gal/GalNAc binding lectin through the substitution of amino-acid residues critical for the binding to sialic acid. Biochem. J. 142, 393–401 (2007)

    Article  CAS  Google Scholar 

  32. Van Damme, E.J.M., Roy, S., Barre, A., Citores, L., Mostafapous, K., Rougé, P., Van Leuven, F., Girbés, T., Goldstein, I.J., Peumans, W.J.: Elderberry (Sambucus nigra) bark contains two structurally different Neu5Ac(α-2,6)Gal/GalNAc-binding type 2 ribosome-inactivating proteins. Eur. J. Biochem. 245, 648–655 (1997)

    Article  PubMed  Google Scholar 

  33. Mo, H., Winter, H.C., Goldstein, I.J.: Purification and characterization of a Neu5Ac α2-6Galβ1-4Glc/GlcNAc-specific lectin from the fruiting body of the polypore mushroom Polyporus squamosus. J. Biol. Chem. 275, 10623–10629 (2000)

    Article  CAS  PubMed  Google Scholar 

  34. Kadirvelraj, R., Grant, O.C., Goldstein, I.J., Winter, H.C., Tateno, H., Fadda, E., Woods, R.J.: Structure and binding analysis of Polyporus squamosus lectin in complex with the Neu5Acα2-6 Galβ1-4GlcNAc human-type influenza receptor. Glycobiology 21, 973–984 (2011)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Yabe, R., Suzuki, R., Kuno, A., Fujimoto, Z., Jigami, Y., Hirabayashi, J.: Tailoring a novel sialic acid-binding lectin from a ricin-B chain-like galactose-binding protein by natural evolution-mimicry. J. Biochem. 141, 389–399 (2007)

    Article  CAS  PubMed  Google Scholar 

  36. Wang, Y., Yu, G., Han, Z., Yang, B., Hu, Y., Zhao, X., Wu, J., Lv, Y., Chai, W.: Specificities of Ricinus communis agglutinin 120 interaction with sulfated galactose. FEBS Lett. 585, 3927–3934 (2011)

    Article  CAS  PubMed  Google Scholar 

  37. Hu, D., Tateno, H., Kuno, A., Yabe, R., Hirabayashi, J.: Directed evolution of lectins with sugar-binding specificity for 6-sulfo-galactose. J. Biol. Chem. 287, 20313–20320 (2012)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Chen, Y., Rougé, P., Peumans, W.J., Van Damme, E.J.M.: Mutational analysis of carbohydrate-binding activity of the NeuAc(α-2,6)Gal/GalNAc-specific type 2 ribosome-inactivating protein from elderberry (Sambucus nigra) fruits. Biochem. J. 364, 587–592 (2002)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Van Damme, E.J.M., Peumans, W.J., Barre, A., Rougé, P.: Plant lectins: a composite of several distinct families of structurally and evolutionary related proteins with diverse biological roles. Crit. Rev. Plt. Sci. 17, 575–692 (1998)

    Article  Google Scholar 

  40. Ferreras, J.M., Citores, L., Iglesias, R., Jiménez, P., Girbés, T: Sambucus ribosome-inactivating proteins and lectins. (Lord, J.M., Hartley, M,R., Eds.), pp.122-123, Chapter 6. Toxic Plant Proteins, Plant Cell Monographs 18, Springer-Verlag Berlin Heidelberg (2010)

  41. Chen, Y., Peumans, W.J., Van Damme, E.J.M.: The Sambucus nigra type-2 ribosome-inactivating protein SNA-I’ exhibits in planta antiviral activity in transgenic tobacco. FEBS J. 516, 27–30 (2002)

    Article  CAS  Google Scholar 

  42. Shahidi Noghabi, S., Van Damme, E.J.M., Smagghe, S.: Carbohydrate-binding activity of the type-2 ribosome-inactivating protein SNA-I from elderberry (Sambucus nigra) is a determining factor for its insecticidal activity. Phytochemistry 69, 2972–2978 (2008)

    Article  CAS  PubMed  Google Scholar 

  43. Shahidi-Noghabi, S., Van Damme, E.J.M., Smagghe, G.: Expression of Sambucus nigra agglutinin (SNA-I’) from elderberry bark in transgenic tobacco plants results in enhanced resistance to different insect species. Transgenic Res. 18, 249–259 (2009)

    Article  CAS  PubMed  Google Scholar 

  44. Battelli, M., Citores, L., Buonamici, L., Ferreras, J.M., De Benito, F.M., Girbés, T., Stirpe, F.: Toxicity and cytotoxicity of nigrin b, a two-chain ribosome-inactivating protein from Sambucus nigra : comparison with ricin. Arch. Toxicol. 71, 360–364 (1997)

    Article  CAS  PubMed  Google Scholar 

  45. Shahidi-Noghabi, S., Van Damme, E.J.M., De Vos, W.H., Smagghe, G.: Internalization of Sambucus nigra agglutinins I and II in insect midgut cells. Arch. Insect Biochem. Physiol. 76, 211–222 (2011)

    Article  CAS  PubMed  Google Scholar 

  46. Shang, C., Madej, M., De Vos, W., Van Damme, E.J.M.: The ribosome-inactivating proteins (RIPs) from elderberry (Sambucus nigra) in the battle against cancer?? Glycoconj. J. 30, 355 (2013)

    Google Scholar 

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Acknowledgments

This work was funded primarily by the Fund for Scientific Research-Flanders (FWO grants G.0022.08) and the Research Council of Ghent University (project BOF10/GOA/003). Chenjing Shang is recipient of China Scholarship Council and receives doctoral co-funding from the Special Research Council of Ghent University. The authors want to thank the Consortium for Functional Glycomics funded by the NIGMS GM62116 for the glycan array analysis. Special thanks to Willy J. Peumans for purification of the proteins and critical reading of the manuscript.

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Shang, C., Van Damme, E.J.M. Comparative analysis of carbohydrate binding properties of Sambucus nigra lectins and ribosome-inactivating proteins. Glycoconj J 31, 345–354 (2014). https://doi.org/10.1007/s10719-014-9527-9

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