Adhesion/Growth-Regulatory Galectins: Insights into Their Ligand Selectivity Using Natural Glycoproteins and Glycotopes

  • Albert M. WuEmail author
  • Tanuja Singh
  • Jia-Hau Liu
  • Sabine André
  • Martin Lensch
  • Hans-Christian Siebert
  • Mickael Krzeminski
  • Alexandre M. J. J. Bonvin
  • Herbert Kaltner
  • June H. Wu
  • Hans-Joachim Gabius
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 705)


“Biochemistry text books commonly make it appear that it is a foregone conclusion that the hardware of biological information storage and transfer is confined to nucleotides and amino acids, the letters of the genetic code. However, the remarkable talents of a third class of biomolecules are often overlooked” [1]. This statement from a recent review guides the readers to look at and fully appreciate the chemical/lectinochemical characteristics of carbohydrates that underlie the concept of the sugar code [2].


Agglutinin Docking Glycosylation Lectin phylogeny Sugar code 



This work was supported by grants from the Chang-Gung Medical Research Project (CMRP No. 33025 and 170441; Kwei-san, Tao-yuan, Taiwan), the National Science Council (NSC 97-2320-B-182-020-MY3 and 97-2628-B-182-002-MY3; Taipei, Taiwan), the Mizutani Foundation for Glycoscience (Tokyo, Japan), the research initiative LMUexcellent (Munich, Germany), the Verein zur Förderung des biologisch-technologischen Fortschritts in der Medizin e. V. (Heidelberg, Germany), and a European Community Marie Curie Research Training Network grant (contract no. MRTN-CT-2005-019561).


  1. 1.
    Gabius HJ, Wu AM (2006) The emerging functionality of endogenous lectins: a primer to the concept and a case study on galectins including medical implications. Chang Gung Med J 29:37–62PubMedGoogle Scholar
  2. 2.
    Gabius HJ (ed) (2009) The sugar code. Fundamentals of glycosciences. Wiley-VCH, WeinheimGoogle Scholar
  3. 3.
    Laine RA (1997) The information-storing potential of the sugar code. In: Gabius HJ, Gabius S (eds) Glycosciences: status and perspectives. Chapman & Hall, London, pp 1–14Google Scholar
  4. 4.
    Brockhausen I, Schachter H (1997) Glycosyltransferases involved in N- and O-glycan biosynthesis. In: Gabius HJ, Gabius S (eds) Glycosciences: status and perspectives. Chapman & Hall, London, pp 79–113Google Scholar
  5. 5.
    Reuter G, Gabius HJ (1999) Eukaryotic glycosylation: whim of nature or multipurpose tool? Cell Mol Life Sci 55:368–422PubMedCrossRefGoogle Scholar
  6. 6.
    Patsos G, Corfield A (2009) O-Glycosylation: structural diversity and functions. In: Gabius HJ (ed) The sugar code. Fundamentals of glycosciences. Wiley-VCH, Weinheim, pp 111–137Google Scholar
  7. 7.
    Wilson IBH, Paschinger K, Rendić D (2009) Glycosylation of model and ‘lower’ organisms. In: Gabius HJ (ed) The sugar code. Fundamentals of glycosciences. Wiley-VCH, Weinheim, pp 139–154Google Scholar
  8. 8.
    Zuber C, Roth J (2009) N-Glycosylation. In: Gabius HJ (ed) The sugar code. Fundamentals of glycosciences. Wiley-VCH, Weinheim, pp 87–110Google Scholar
  9. 9.
    Lemieux RU (1989) The origin of the specificity in the recognition of oligosaccharides by proteins. Chem Soc Rev 18:347–374CrossRefGoogle Scholar
  10. 10.
    Lemieux RU (1996) How water provides the impetus for molecular recognition in aqueous solution. Acc Chem Res 29:373–380CrossRefGoogle Scholar
  11. 11.
    Gabius HJ (1998) The how and why of protein–carbohydrate interaction: a primer to the theoretical concept and a guide to application in drug design. Pharm Res 15:23–30PubMedCrossRefGoogle Scholar
  12. 12.
    Gabius HJ, Siebert HC, André S, Jiménez-Barbero J, Rüdiger H (2004) Chemical biology of the sugar code. Chembiochem 5:740–764PubMedCrossRefGoogle Scholar
  13. 13.
    Solís D, Romero A, Menéndez M, Jiménez-Barbero J (2009) Protein–carbohydrate ­interactions: basic concepts and methods for analysis. In: Gabius HJ (ed) The sugar code. Fundamentals of glycosciences. Wiley-VCH, Weinheim, pp 233–245Google Scholar
  14. 14.
    Watkins WM, Morgan WTJ (1952) Neutralisation of the anti-H agglutinin in eel serum by simple sugars. Nature 169:825–826PubMedCrossRefGoogle Scholar
  15. 15.
    Kilpatrick DC, Green C (1992) Lectins as blood typing reagents. Adv Lectin Res 5:51–94Google Scholar
  16. 16.
    Watkins WM (1999) A half century of blood-group antigen research: some personal recollections. Trends Glycosci Glycotechnol 11:391–411Google Scholar
  17. 17.
    Rüdiger H, Gabius HJ (2009) The history of lectinology. In: Gabius HJ (ed) The sugar code. Fundamentals of glycosciences. Wiley-VCH, Weinheim, pp 261–268Google Scholar
  18. 18.
    von der Lieth CW, Siebert HC, Kožár T, Burchert M, Frank M, Gilleron M, Kaltner H, Kayser G, Tajkhorshid E, Bovin NV, Vliegenthart JFG, Gabius HJ (1998) Lectin ligands: new insights into their conformations and their dynamic behavior and the discovery of conformer selection by lectins. Acta Anat 161:91–109PubMedCrossRefGoogle Scholar
  19. 19.
    López-Lucendo MF, Solís D, André S, Hirabayashi J, Kasai KI, Kaltner H, Gabius HJ, Romero A (2004) Growth-regulatory human galectin-1: crystallographic characterisation of structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. J Mol Biol 343:957–970PubMedCrossRefGoogle Scholar
  20. 20.
    Siebert HC, André S, Lu SY, Frank M, Kaltner H, van Kuik JA, Korchagina EY, Bovin NV, Tajkhorshid E, Kaptein R, Vliegenthart JFG, von der Lieth CW, Jiménez-Barbero J, Kopitz J, Gabius HJ (2003) Unique conformer selection of human growth-regulatory lectin galectin-1 for ganglioside GM1 versus bacterial toxins. Biochemistry 42:14762–14773PubMedCrossRefGoogle Scholar
  21. 21.
    André S, Kaltner H, Lensch M, Russwurm R, Siebert HC, Fallsehr C, Tajkhorshid E, Heck AJR, von Knebel DM, Gabius HJ, Kopitz J (2005) Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells. Int J Cancer 114:46–57PubMedCrossRefGoogle Scholar
  22. 22.
    Kopitz J, von Reitzenstein C, Burchert M, Cantz M, Gabius HJ (1998) Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture. J Biol Chem 273:11205–11211PubMedCrossRefGoogle Scholar
  23. 23.
    Kopitz J, von Reitzenstein C, André S, Kaltner H, Uhl J, Ehemann V, Cantz M, Gabius HJ (2001) Negative regulation of neuroblastoma cell growth by carbohydrate-dependent surface binding of galectin-1 and functional divergence from galectin-3. J Biol Chem 276:35917–35923PubMedCrossRefGoogle Scholar
  24. 24.
    Wang J, Lu ZH, Gabius HJ, Rohowsky-Kochan C, Ledeen RW, Wu G (2009) Cross-linking of GM1 ganglioside by galectin-1 mediates regulatory T cell activity involving TRPC5 channel activation: possible role in suppressing experimental autoimmune encephalomyelitis. J Immunol 182:4036–4045PubMedCrossRefGoogle Scholar
  25. 25.
    Siebert HC, Gilleron M, Kaltner H, von der Lieth CW, Kožár T, Bovin NV, Korchagina EY, Vliegenthart JFG, Gabius HJ (1996) NMR-based, molecular dynamics- and random walk molecular mechanics-supported study of conformational aspects of a carbohydrate ligand (Galβ1-2Galβ1-R) for an animal galectin in the free and in the bound state. Biochem Biophys Res Commun 219:205–212PubMedCrossRefGoogle Scholar
  26. 26.
    Gilleron M, Siebert HC, Kaltner H, von der Lieth CW, Kožár T, Halkes KM, Korchagina EY, Bovin NV, Gabius HJ, Vliegenthart JFG (1998) Conformer selection and differential restriction of ligand mobility by a plant lectin. Conformational behavior of Galβ1-3GlcNAcβ1-R, Galβ1-3GalNAcβ1-R and Galβ1-2Galβ1-R’ in the free state and complexed with mistletoe lectin as revealed by random walk and conformational clustering molecular mechanics calculations, molecular dynamics simulations and nuclear Overhauser experiments. Eur J Biochem 252:416–427PubMedCrossRefGoogle Scholar
  27. 27.
    Kaltner H, Gabius HJ (2001) Animal lectins: from initial description to elaborated structural and functional classification. In: Wu AM (ed) The molecular immunology of complex carbohydrates. Adv Exp Med Biol, vol 491. Plenum Press, New York, pp 79–93Google Scholar
  28. 28.
    Cooper DNW (2002) Galectinomics: finding themes in complexity. Biochim Biophys Acta 1572:209–231PubMedGoogle Scholar
  29. 29.
    Rappl G, Abken H, Muche JM, Sterry W, Tilgen W, André S, Kaltner H, Ugurel S, Gabius HJ, Reinhold U (2002) CD4+CD7 leukemic T cells from patients with Sézary syndrome are protected from galectin-1-triggered T cell death. Leukemia 16:840–845PubMedCrossRefGoogle Scholar
  30. 30.
    André S, Sanchez-Ruderisch H, Nakagawa H, Buchholz M, Kopitz J, Forberich P, Kemmner W, Böck C, Deguchi K, Detjen KM, Wiedenmann B, von Knebel DM, Gress TM, Nishimura SI, Rosewicz S, Gabius HJ (2007) Tumor suppressor p16INK4a: modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate dependent induction of anoikis in pancreatic carcinoma cells. FEBS J 274:3233–3256PubMedCrossRefGoogle Scholar
  31. 31.
    Roda O, Ortiz-Zapater E, Martínez-Bosch N, Gutiérrez-Gallego R, Vila-Perelló M, Ampurdanés C, Gabius HJ, André S, Andreu D, Real FX, Navarro P (2009) Galectin-1 is a novel functional receptor for tissue plasminogen activator in pancreatic cancer. Gastroenterology 136:1379–1390PubMedCrossRefGoogle Scholar
  32. 32.
    Ahmad N, Gabius HJ, Kaltner H, André S, Kuwabara I, Liu FT, Oscarson S, Norberg T, Brewer CF (2002) Thermodynamic binding studies of cell surface carbohydrate epitopes to galectins-1, -3, and -7: evidence for differential binding specificities. Can J Chem 80:1096–1104CrossRefGoogle Scholar
  33. 33.
    Wu AM (2003) Carbohydrate structural units in glycoproteins and polysaccharides as ­important ligands for Gal and GalNAc reactive lectins. J Biomed Sci 10:676–688PubMedCrossRefGoogle Scholar
  34. 34.
    Purkrábková T, Smetana K Jr, Dvořánková B, Holíková Z, Böck C, Lensch M, André S, Pytlík R, Liu FT, Klíma J, Smetana K, Motlík J, Gabius HJ (2003) New aspects of galectin functionality in nuclei of cultured bone marrow stromal and epidermal cells: biotinylated galectins as tool to detect specific binding sites. Biol Cell 95:535–545PubMedCrossRefGoogle Scholar
  35. 35.
    Kübler D, Hung CW, Dam TK, Kopitz J, André S, Kaltner H, Lohr M, Manning JC, He L, Wang H, Middelberg A, Brewer CF, Reed J, Lehmann WD, Gabius HJ (2008) Phosphorylated human galectin-3: facile large-scale preparation of active lectin and detection of structural changes by CD spectroscopy. Biochim Biophys Acta 1780:716–722PubMedGoogle Scholar
  36. 36.
    Wu AM, Singh T, Wu JH, Lensch M, André S, Gabius HJ (2006) Interaction profile of ­galectin-5 with free saccharides and mammalian glycoproteins: probing its fine specificity and the effect of naturally clustered ligand presentation. Glycobiology 16:524–537PubMedCrossRefGoogle Scholar
  37. 37.
    Wu AM, Wu JH, Liu JH, Singh T, André S, Kaltner H, Gabius HJ (2004) Effects of polyvalency of glycotopes and natural modifications of human blood group ABH/Lewis sugars at the Galβ1-terminated core saccharides on the binding of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N). Biochimie 86:317–326PubMedCrossRefGoogle Scholar
  38. 38.
    Wu AM, Wu JH, Tsai MS, Liu JH, André S, Wasano K, Kaltner H, Gabius HJ (2002) Fine specificity of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N). Biochem J 367:653–664PubMedCrossRefGoogle Scholar
  39. 39.
    Wu JH, Singh T, Herp A, Wu AM (2006) Carbohydrate recognition factors of the lectin domains present in the Ricinus communis toxic protein (ricin). Biochimie 88:201–217PubMedCrossRefGoogle Scholar
  40. 40.
    Kaltner H, Solís D, Kopitz J, Lensch M, Lohr M, Manning JC, Mürnseer M, Schnölzer M, André S, Sáiz JL, Gabius HJ (2008) Prototype chicken galectins revisited: characterization of a third protein with distinctive hydrodynamic behaviour and expression pattern in organs of adult animals. Biochem J 409:591–599PubMedCrossRefGoogle Scholar
  41. 41.
    Varela PF, Solís D, Díaz-Mauriño T, Kaltner H, Gabius HJ, Romero A (1999) The 2.15  Å crystal structure of CG-16, the developmentally regulated homodimeric chicken galectin. J Mol Biol 294:537–549PubMedCrossRefGoogle Scholar
  42. 42.
    López-Lucendo MF, Solís D, Sáiz JL, Kaltner H, Russwurm R, André S, Gabius HJ, Romero A (2009) Homodimeric chicken galectin CG-1B (C-14): crystal structure and detection of unique redox-dependent shape changes involving inter-and intrasubunit disulfide bridges by gel filtration, ultracentrifugation, site-directed mutagenesis and peptide mass fingerprinting. J Mol Biol 386:366–378PubMedCrossRefGoogle Scholar
  43. 43.
    Sakakura Y, Hirabayashi J, Oda Y, Ohyama Y, Kasai KI (1990) Structure of chicken 16-kDa β-galactoside-binding lectin: complete amino acid sequence, cloning of cDNA and production of recombinant lectin. J Biol Chem 265:21573–21579PubMedGoogle Scholar
  44. 44.
    Wu AM, Wu JH, Tsai MS, Kaltner H, Gabius HJ (2001) Carbohydrate specificity of a galectin from chicken liver (CG-16). Biochem J 358:529–538PubMedCrossRefGoogle Scholar
  45. 45.
    Wu AM, Singh T, Liu JH, Krzeminski M, Russwurm R, Siebert HC, Bonvin AMJJ, André S, Gabius HJ (2007) Activity–structure correlations in divergent lectin evolution: fine specificity of chicken galectin CG-14 and computational analysis of flexible ligand docking for CG-14 and the closely related CG-16. Glycobiology 17:165–184PubMedCrossRefGoogle Scholar
  46. 46.
    Dominguez C, Boelens R, Bonvin AMJJ (2003) HADDOCK: a protein–protein docking approach based on biochemical or biophysical information. J Am Chem Soc 125:1731–1737PubMedCrossRefGoogle Scholar
  47. 47.
    Villalobo A, Nogales-González A, Gabius HJ (2006) A guide to signaling pathways connecting protein–glycan interaction with the emerging versatile effector functionality of mammalian lectins. Trends Glycosci Glycotechnol 18:1–37Google Scholar
  48. 48.
    Gabius HJ (2008) Glycans: bioactive signals decoded by lectin. Biochem Soc Trans 36:1491–1496PubMedCrossRefGoogle Scholar
  49. 49.
    Rüdiger H, Siebert HC, Solís D, Jiménez-Barbero J, Romero A, von der Lieth CW, ­Díaz-Mauriño T, Gabius HJ (2000) Medicinal chemistry based on the sugar code: fundamentals of lectinology and experimental strategies with lectins as targets. Curr Med Chem 7:389–416PubMedGoogle Scholar
  50. 50.
    Yamazaki N, Kojima S, Bovin NV, André S, Gabius S, Gabius HJ (2000) Endogenous lectins as targets for drug delivery. Adv Drug Deliv Rev 43:225–244PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Albert M. Wu
    • 1
    Email author
  • Tanuja Singh
  • Jia-Hau Liu
  • Sabine André
  • Martin Lensch
  • Hans-Christian Siebert
  • Mickael Krzeminski
  • Alexandre M. J. J. Bonvin
  • Herbert Kaltner
  • June H. Wu
  • Hans-Joachim Gabius
  1. 1.Glyco-Immunochemistry Research Laboratory, Institute of Molecular and Cellular Biology, College of MedicineChang-Gung UniversityKwei-Shan, Tao-YuanTaiwan

Personalised recommendations