Lectins Are Specific CarbohydrateBinding Proteins

Figure 11.27. Mass Spectrometric "Sequencing" of Oligosaccharides. Carbohydrate-cleaving enzymes were used to
release and specifically cleave the oligosaccharide component of the glycoprotein fetuin from bovine serum. Parts A and
B show the masses obtained with MALDI-TOF spectrometry as well as the corresponding structures of the
oligosaccharide digestion products (using the same scheme as that in Figure 11.19): (A) digestion with Peptide Nglycosidase F (to release the oligosaccharide from the protein) and neuraminidase; (B) digestion with Peptide Nglycosidase F, neuraminidase, and β-1,4-galactosidase. Knowledge of the enzyme specificities and the masses of the
products permits the characterization of the oligosaccharide. [After A. Varki, R. Cummings, J. Esko, H. Freeze, G. Hart,
and J. Marth (Eds.), Essentials of Glycobiology (Cold Spring Harbor Laboratory Press, 1999), p. 596.]
I. The Molecular Design of Life
11. Carbohydrates
11.4. Lectins Are Specific Carbohydrate-Binding Proteins
The diverse carbohydrate structures displayed on cell surfaces are well suited to serve as interaction sites between cells
and their environments. Proteins termed lectins (from the Latin legere, "to select") are the partners that bind specific
carbohydrate structures. Lectins are ubiquitous, being found in animals, plants, and microorganisms. We have already
seen that some lectins, such as calnexin, function as chaperones in protein folding (Section 11.3.6).
11.4.1. Lectins Promote Interactions Between Cells
The chief function of lectins in animals is to facilitate cell-cell contact. A lectin usually contains two or more binding
sites for carbohydrate units; some lectins form oligomeric structures with multiple binding sites. The binding sites of
lectins on the surface of one cell interact with arrays of carbohydrates displayed on the surface of another cell. Lectins
and carbohydrates are linked by a number of relatively weak interactions that ensure specificity yet permit unlinking as
needed. The interactions between one cell surface with carbohydrates and another with lectins resemble the action of
Velcro; each interaction is relatively weak but the composite is strong.
The exact role of lectins in plants is unclear, although they can serve as potent insecticides. Castor beans contain so
much lectin that they are toxic to most organisms. The binding specificities of lectins from plants have been well
characterized (Figure 11.28). Bacteria, too, contain lectins. Escherichia coli bacteria are able to adhere to epithelial cells
of the gastrointestinal tract because lectins on the E. coli surface recognize oligosaccharide units on the surfaces of target
cells. These lectins are located on slender hairlike appendages called fimbriae (pili).
Lectins can be divided into classes on the basis of their amino acid sequences and biochemical properties. One large
class is the C type (for calcium-requiring) found in animals. These proteins have in common a domain of 120 amino
acids that is responsible for carbohydrate binding. The structure of one such domain bound to a carbohydrate target is
shown in Figure 11.29. A calcium ion acts as a bridge between the protein and the sugar through direct interactions with
sugar hydroxyl groups. In addition, two glutamate residues in the protein bind to both the calcium ion and the sugar,
while other protein side chains form hydrogen bonds with other hydroxyl groups on the carbohydrate. Changes in the
amino acid residues that interact with the carbohydrate alter the carbohydrate-binding specificity of the lectin.
Proteins termed selectins are members of the C-type family. Selectins bind immune-system cells to the sites of
injury in the inflammatory response (Figure 11.30). The L, E, and P forms of selectins bind specifically to
carbohydrates on lymph-node vessels, endothelium, or activated blood platelets, respectively. New therapeutic agents
that control inflammation may emerge from a deeper understanding of how selectins bind and distinguish different
carbohydrates.
11.4.2. Influenza Virus Binds to Sialic Acid Residues
The ability of viruses to infect specific cell types is dictated in part by the ability of these viruses to bind to
particular structures or receptors on the surfaces of cells. In some cases, these receptors are carbohydrates. For
example, influenza virus recognizes sialic acid residues present on cell-surface glycoproteins. The viral protein that binds
to these sugars is called hemagglutinin(Figure 11.31).
After these surface interactions have taken place and the virus has been taken into the cell, another viral protein,
neuramidase, cleaves the glycosidic bonds to the sialic acid residues, freeing the virus to infect the cell. Inhibitors of this
enzyme are showing some promise as anti-influenza agents.
I. The Molecular Design of Life
11. Carbohydrates
11.4. Lectins Are Specific Carbohydrate-Binding Proteins
Figure 11.28. Binding Selectivities of Plant Lectins. The plant lectins wheat germ agglutinin, peanut lectin, and
phytohemagglutinin recognize different oligosaccharides.
I. The Molecular Design of Life
11. Carbohydrates
11.4. Lectins Are Specific Carbohydrate-Binding Proteins
Figure 11.29. Structure of a C-Type Carbohydrate-Binding Domain from an Animal Lectin. A calcium ion links a
mannose residue to the lectin. Selected interactions are shown, with some hydrogen atoms omitted for clarity.
I. The Molecular Design of Life
11. Carbohydrates
11.4. Lectins Are Specific Carbohydrate-Binding Proteins
Figure 11.30. Selectins Mediate Cell-Cell Interactions. The scanning electron micrograph shows lymphocytes
adhering to the endothelial lining of a lymph node. The L selectins on the lymphocyte surface bind specifically to
carbohydrates on the lining of the lymph-node vessels. [Courtesy of Dr. Eugene Butcher.]