Lectins

Abstract

Lectins, a class of sugar‐specific and cell‐agglutinating proteins of nonimmune origin that are devoid of enzymatic activity, are ubiquitous in nature. Plant lectins are invaluable tools for the study of carbohydrates, in solution and on cells, and are also employed for purging of bone marrow for transplantation into ‘bubble children’. Bacterial cell surface lectins mediate the attachment of the organisms to host cell surfaces in the initiation of infection; their blocking by suitable sugars can serve as a basis of antiadhesion therapy of bacterial diseases. Those of animals control the biosynthesis of glycoproteins, play key roles in cell interactions in the immune system and serve as innate immunity agents against microbial pathogens. They also monitor the migration of leucocytes in blood vessels and contribute to proliferation and metastasis of tumour cells.

Key concepts:

  • Antiadhesion therapy

  • Carbohydrate specificity

  • Cell recognition

  • Circular homology

  • Glycoarrays; lectin arrays

  • Lectin replacement therapy

  • Surface carbohydrates

  • Multisubunit proteins

Keywords: adhesion; carbohydrates; combining sites; glycoproteins; recognition

Figure 1.

Structures of different lectins represented as ribbon diagrams. (a) Upper row shows monomers of plant (concanavalin A) and animal lectins (ERGIC‐53, human galectin‐7 and serum amyloid protein) that share the jellyroll or lectin fold. First three (from left) in the lower row all exhibit the β‐trefoil fold; the first two of these are from plants, the third (and the fourth) from animals. (b) Variations in quaternary lectin structures. In all figures, the grey spheres represent metal ions; bound carbohydrate is shown in ball and stick representation. Reprinted with permission from Loris R (2002) Principles of structures of animal and plant lectins. Biochimica et Biophysica Acta1572: 198–208. Elsevier, Oxford.

Figure 2.

(a) Binding site of legume lectins. Key hydrogen bonds with amino acid side chains (dotted lines) holding galactose (red lines) in the combining site of a galactose‐specific lectin (e.g. from the coral tree) and glucose (solid line) in a glucose‐/mannose‐specific lectin (e.g. concanavalin A or pea lectin). (b) N‐acetylneuraminic acid in the combining site of wheat germ agglutinin.

Figure 3.

Schematic representation of the precursors of soybean agglutinin (pre‐SBA), concanavalin A (pre‐ConA), wheat germ agglutinin (pre‐WGA) and ricin (pre‐ricin) and of their processing to the mature lectins. Arrows denote positions of cleavages, and numbers in parentheses in pre‐ConA give the corresponding positions in mature concanavalin A. Processing of pro‐SBA and pro‐WGA (like that of the precursors of most legume and cereal lectins) involves sequential cleavage of the signal peptide and of the C‐terminal peptide (which in the cereal lectins is glycosylated). Pre‐ConA contains in addition to the earlier peptides a glycosylated spacer. After removal of the signal peptide, the precursor is deglycosylated; an endopeptidase then cleaves the spacer and residues 118 and 119 are ligated enzymatically, with the concomitant removal of the C‐terminal peptide, resulting in the rearrangement of the primary sequence of the precursor. In pro‐ricin, the polypeptides of the two subunits (A and B) are separated by a spacer peptide, but already linked by an S–S bridge, and processing involves the cleavage of the signal peptide, the C‐terminal and the spacer peptides (N‐linked oligosaccharide).

Figure 4.

N‐Acetylneuraminic acid in the combining site of influenza virus lectin.

Figure 5.

Combining sites of animal lectins. (a) Bovine galectin with bound galactose. (b) Mannose‐binding protein with bound mannose. Hydrogen bonds are shown as broken lines and coordination bonds as dotted lines.

Figure 6.

Schematic representation of the multidomain structure of the selectins. CR, complement regulatory repeats; EFG, epidermal growth factor‐like repeats and CRD, carbohydrate‐recognition domain. Structures on top are of the selectin ligands.

Figure 7.

Bouquet‐like structure of MBP with mannose oligosaccharides bound to its three carbohydrate recognition. The green and white circles next to the sites denote differently attached calcium ions. COL, collagenous region and CRD, carbohydrate‐recognition domain. Reprinted with permission from Weis WI and Drickamer K (1994) Trimeric structure of a C‐type mannose‐binding protein. Structure2: 1227–1240.

Figure 8.

Surface lectins mediate cell adhesion by binding to corresponding carbohydrates on apposing cells. Reproduced from Sharon and Lis (1993) Carbohydrates in cell recognition. Scientific American268(1): 82–89.

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Further Reading

Blixt O, Head S, Mondala T et al. (2004) Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proceedings of the National Academy of Sciences of the USA 101: 17033–17038.

Dommett RM, Klein N and Turner MW (2006) Mannose‐binding lectin in innate immunity: past, present and future. Tissue Antigens 68: 193–209.

Kilpatrick DC (2002) Animal lectins: a historical introduction and overview. Biochimica et Biophysica Acta 1572: 187–197.

Rosenfeld R, Bangio H, Gerwig GJ et al. (2007) A lectin array‐based methodology for the analysis of protein glycosylation. Journal of Biochemical and Biophysical Methods 70: 415–426.

Sharon N (2006) Carbohydrates as future anti‐adhesion drugs for infectious diseases. Biochimica et Biophysica Acta 1760: 527–537.

Sharon N and Lis H (2003) Lectins, 2nd edn, 454pp. Dordrecht, The Netherlands: Kluwer Academic Publishers.

Sharon N and Lis H (2004) History of lectins: from hemagglutinins to biological recognition molecules. Glycobiology 14: 53R–63R.

Taylor ME and Drickamer K (2007) Paradigms for glycan‐binding receptors in cell adhesion. Current Opinion in Cell Biology 19: 572–577.

Van Damme EJM, Peumans WJ, Pusztai A and Bardocz S (1998) Handbook of Plant Lectins: Properties and Biomedical Applications, 452pp. Chichester: Wiley.

Van Kooyk Y and Rabinovich GA (2008) Protein‐glycan interactions in the control of innate and adaptive immune responses. Nature Immunology 9: 593–601.

Wellens A, Garofalo C, Nguyen H et al. (2008) Intervening with urinary tract infections using anti‐adhesives based on the crystal structure of the fimH–oligomannose‐3 complex. PLoS 3: e2040.

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How to Cite close
Sharon, Nathan(Sep 2009) Lectins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000708.pub2]