7.4 Carbohydrates as Informational Molecules: The Sugar Code in Chapter 7 Carbohydrates and Glycobiology

Oligosaccharide Structures Are Information-Dense

Improved methods for the analysis of oligosaccharide and polysaccharide structure have revealed remarkable complexity and diversity in the oligosaccharides of glycoproteins and glycolipids. Consider the oligosaccharide chains in Figure 7-27, typical of those found in many glycoproteins. The most complex of those shown contains 14 monosaccharide residues of four different kinds, variously linked as $(1 → 2)$ $left-parenthesis 1 right-arrow 2 right-parenthesis$ , $(1 → 3)$ $left-parenthesis 1 right-arrow 3 right-parenthesis$ , $(1 → 4)$ $left-parenthesis 1 right-arrow 4 right-parenthesis$ , $(1 → 6)$ $left-parenthesis 1 right-arrow 6 right-parenthesis$ , $(2 → 3)$ $left-parenthesis 2 right-arrow 3 right-parenthesis$ , and $(2 → 6)$ $left-parenthesis 2 right-arrow 6 right-parenthesis$ , some with the α and some with the β configuration. Branched structures, not found in nucleic acids or proteins, are common in oligosaccharides. With the reasonable assumption that 20 different monosaccharide subunits are available for construction of oligosaccharides, we can calculate that many billions of different hexameric oligosaccharides are possible; this compares with $6.4 \times 10^{7} (20^{6})$ $6.4 times 10 Superscript 7 Baseline left-parenthesis 20 Superscript 6 Baseline right-parenthesis$ different hexapeptides possible for the 20 common amino acids, and 4,096 $(4^{6})$ $left-parenthesis 4 Superscript 6 Baseline right-parenthesis$ different hexanucleotides for the four nucleotide subunits. If we also allow for variations in oligosaccharides resulting from sulfation of one or more residues, the number of possible oligosaccharides increases by two orders of magnitude. In reality, only a subset of possible combinations is found, given the restrictions imposed by the biosynthetic enzymes and the availability of precursors. Nevertheless, the enormously rich structural information in glycans does not merely rival but far surpasses that of nucleic acids in the density of information contained in a molecule of modest size. Each of the oligosaccharides represented in Figures 7-20 and 7-27 presents a unique, three-dimensional face — a word in the sugar code — readable by the proteins that interact with it.

Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes

Lectins bind carbohydrates with high specificity and with moderate to high affinity. These proteins serve in a wide variety of cell-cell recognition, signaling, and adhesion processes and in intracellular targeting of newly synthesized proteins. Plant lectins, abundant in seeds, probably serve as deterrents to insects and other predators. In the laboratory, purified plant lectins are useful reagents for detecting and separating glycans and glycoproteins with different oligosaccharide moieties. Here we discuss just a few examples of the roles of lectins in animal cells.

Some peptide hormones that circulate in the blood have oligosaccharide moieties that strongly influence their circulatory half-life. Luteinizing hormone and thyrotropin (polypeptide hormones produced in the pituitary) have N-linked oligosaccharides that end with the disaccharide GalNAc4S $(β 1 → 4) Glc$ $left-parenthesis beta Baseline 1 right-arrow 4 right-parenthesis Glc$ NAc, which is recognized by a lectin (receptor) of hepatocytes. (GalNAc4S is N-acetylgalactosamine sulfated on the —OH group at C-4.) Receptor-hormone interaction mediates the uptake and destruction of luteinizing hormone and thyrotropin, reducing their concentration in the blood. Thus the blood levels of these hormones undergo a periodic rise (due to pulsatile secretion by the pituitary) and fall (due to constant destruction by hepatocytes).

Residues of Neu5Ac (a sialic acid) situated at the ends of the oligosaccharide chains of many plasma glycoproteins (Fig. 7-20) protect these proteins from uptake and degradation in the liver. For example, ceruloplasmin, a copper-containing serum glycoprotein, has several oligosaccharide chains ending in Neu5Ac. The mechanism that removes sialic acid residues from serum glycoproteins is unclear. It may be due to the activity of the enzyme neuraminidase (also called sialidase) produced by invading organisms or to a steady, slow release of the residues by extracellular enzymes. The plasma membrane of hepatocytes has lectin molecules (asialoglycoprotein receptors; “asialo-” indicating “without sialic acid”) that specifically bind oligosaccharide chains with galactose residues no longer “protected” by a terminal Neu5Ac residue. Receptor-ceruloplasmin interaction triggers endocytosis and destruction of the ceruloplasmin.

A figure shows the structure of N-acetylneuraminic acid (N lowercase E U 5 uppercase A lowercase C) (a sialic acid).

The molecule has a six-membered ring with O at the position between C 5 and C 1. It is shown as a chair shape with C 1 up and C 4 down. C 1 is vertically bonded to C O O H above the ring and bonded to O H at an angle below the ring; C 2 is bonded to H vertically below the ring and at an angle above the ring; C 3 is bonded to H vertically above the ring and O H at an angle below the ring; C 4 is bonded to N H above the ring at an angle that is further bonded to C that is double bonded to O and bonded to C H 3; C 4 is also bonded to H vertically below the ring; C 5 is bonded to H vertically above the ring and to C at an angle below the ring that is hashed wedge bonded to O H to the front left, to H at the left, and to C above that is hashed wedge bonded to H behind, bonded to C H 2 O H to the upper left, and bonded to O H above.

A similar mechanism is apparently responsible for removing “old” erythrocytes from the mammalian bloodstream. Newly synthesized erythrocytes have several membrane glycoproteins with oligosaccharide chains that end in Neu5Ac. In the laboratory, when the sialic acid residues are removed by withdrawing a sample of blood from experimental animals, treating it with neuraminidase in vitro, and reintroducing it into the circulation, the treated erythrocytes disappear from the bloodstream within a few hours; erythrocytes with intact oligosaccharides (withdrawn and reintroduced without neuraminidase treatment) continue to circulate for days.

Selectins are a family of plasma membrane lectins that mediate cell-cell recognition and adhesion in a wide range of cellular processes. One such process is the movement of immune cells (leukocytes) through the capillary wall, from blood to tissues, at sites of infection or inflammation (Fig. 7-29). At an infection site, P-selectin on the surface of capillary endothelial cells interacts with a specific oligosaccharide of the surface glycoproteins of circulating leukocytes. This interaction slows the leukocytes as they roll along the endothelial lining of the capillaries. A second interaction, between integrin molecules in the leukocyte plasma membrane and an adhesion protein on the endothelial cell surface, now stops the leukocyte and allows it to move through the capillary wall into the infected tissues to initiate the immune attack. Two other selectins participate in this “lymphocyte homing”: E-selectin on the endothelial cell and l-selectin on the leukocyte bind their cognate oligosaccharides on the leukocyte and endothelial cell, respectively. Several of the selectins essential to lymphocyte homing bind specifically to the tetrasaccharide $Neu5Ac- (α 2 → 3) - D -Gal- (β 1 → 4)$ $Neu 5 Ac hyphen left-parenthesis alpha Baseline 2 right-arrow 3 right-parenthesis hyphen upper D hyphen Gal hyphen left-parenthesis beta Baseline 1 right-arrow 4 right-parenthesis$ $(α - L -Fuc- [1 → 4]) - D -GlcNAc$ $left-parenthesis alpha hyphen upper L hyphen Fuc hyphen left-bracket 1 right-arrow 4 right-bracket right-parenthesis hyphen upper D hyphen GlcNAc$ , called sialyl Lewis x or sialyl ${Le}^{x}$ $Le Superscript x$ .

A figure shows how lectin-ligand interactions are involved in leukocyte movement to a site of injury. — FIGURE 7-29 Role of lectin-ligand interactions in leukocyte movement to the site of an infection or injury. A leukocyte circulating through a capillary is slowed by transient interactions between P-selectin molecules in the plasma membrane of the capillary endothelial cells and glycoprotein ligands for P-selectin on the leukocyte surface. As the leukocyte interacts with successive P-selectin molecules, it rolls along the capillary surface. Near a site of inflammation, stronger interactions between integrin in the leukocyte surface and its ligand in the capillary surface lead to tight adhesion. The leukocyte stops rolling and, under the influence of signals from the site of inflammation (such as sialyl Lewis x), escapes through the capillary wall as it moves toward the region of inflammation.

A horizontal blood vessel is cut open so that the interior is visible. Blood flows toward the right, and horizontal bars representing epithelial cells are shown along the top and bottom sides. The region beneath the blood vessel is labeled subendothelial matrix. Tiny rods with small balls on top project from the epithelial cells into the lumen and are labeled glycoprotein ligand for integrin. Larger Y-shaped structures project from the epithelial cells and are labeled P selectin. A leukocyte is shown as a sphere at the upper left. It has four pairs of integrins evenly spaced on its surface, each integrin having a tail extending into the cell and a larger oval head at the opposite end. Evenly spaced between the paired integrins, small rods extend out to small spheres and are labeled glycoprotein ligand for P selectin. Two steps, tethering and rolling, occur under the heading selectin binding. Tethering: An arrow shows that the leukocyte moves down and one of the yellow spheres inserts into the fork of P selectin. Rolling: An arrow shows that the bound leukocyte rotates clockwise. The next two steps, slow rolling and arrest, are shown under the heading integrin binding. In slow rolling, an arrow shows that the leukocyte rotates further clockwise so that the glycoprotein ligand leaves P selectin and two heads of a pair of integrins attach to a glycoprotein ligand for integrin. A second pair of integrin heads attach to an adjacent glycoprotein ligand for binding, causing the cell to stretch so it is narrower at this location. Arrest: The cell is circular again with a pair of integrins bound to a glycoprotein ligand on each side of a glycoprotein bound to P selectin at the bottom center of the molecule. Two additional steps are shown without a heading. Adhesion: the leukocyte extends into an irregular shape with one narrow end. The bottom of the cell pushes into the endothelial cell. Extravasation: the cell pushes between two endothelial cells. It is narrow between the cells and rounded beneath, where it extends into a reddened semicircle labeled site of inflammation.

Human selectins mediate the inflammatory responses in rheumatoid arthritis, asthma, psoriasis, multiple sclerosis, and the rejection of transplanted organs, and thus there is great interest in developing drugs that inhibit selectin-mediated cell adhesion. Many carcinomas express sialyl Lewis x, which, when shed into the circulation, facilitates tumor cell survival and metastasis. Carbohydrate derivatives that mimic the sialyl Lewis x portion of sialoglycoproteins and compete for specific selectin-binding sites, or that alter the biosynthesis of the oligosaccharide, might prove effective as selectin-specific drugs for treating chronic inflammation or metastatic disease.

Several animal viruses, including the influenza virus, attach to their host cells through interactions with oligosaccharides displayed on the host cell surface. The lectin of the influenza virus, known as the HA (hemagglutinin) protein, is essential for viral entry and infection. After the virus has entered a host cell and has been replicated, the newly synthesized viral particles bud out of the cell, wrapped in a portion of its plasma membrane. A viral sialidase (neuraminidase) trims the terminal sialic acid residue from the host cell’s oligosaccharides, releasing the viral particles from their interaction with the cell and preventing their aggregation with one another. Another round of infection can now begin. The antiviral drugs oseltamivir (Tamiflu) and zanamivir (Relenza) are used clinically in the treatment of influenza. These drugs are sugar analogs; they inhibit the viral sialidase by competing with the host cell’s oligosaccharides for binding (Fig. 7-30). This prevents the release of viruses from the infected cell by sialidase, and also causes viral particles to aggregate, both of which block another cycle of infection.

A four-part figure, a, b, c, and d, shows the binding site on the influenza neuraminidase for N-acetylneuraminic acid and an antiviral drug. — FIGURE 7-30 Binding site on influenza neuraminidase for N-acetylneuraminic acid and an antiviral drug. (a) The normal binding ligand for influenza neuraminidase is a sialic acid, N-acetylneuraminic acid. The drugs oseltamivir and zanamivir occupy the same site on the enzyme, competitively inhibiting it and blocking viral release from the host cell. (b) The normal interaction with N-acetylneuraminic acid in the binding site. (c) Oseltamivir can fit into this site by pushing a nearby Glu residue out of the way. (d) A mutation in the influenza virus’s gene for neuraminidase replaces a His near this Glu residue with the larger side chain of a Tyr. Now, oseltamivir is not as effective at pushing the Glu out of its way, and the drug binds much less well to the binding site, making the mutant virus effectively resistant to oseltamivir. [Data from (b) PDB ID 2BAT, J. N. Varghese et al., *Proteins* 14:327, 1992; (c) PDB ID 2HU4, R. J. Russell et al., *Nature* 443:45, 2006; (d) PDB ID 3CL0, P. J. Collins et al., *Nature* 453:1258, 2008.]

Part a shows the molecular structures of N-acetylneuraminic acid, oseltamivir, and zanamivir. All have a ring. N-acetylneuraminic acid and zanamivir both have rings that contain O. Each molecule has several substituents, including chains. Part b shows a bumpy, irregular background with N-acetylneuraminic acid visible within a pocket in the surface. A chain extends upward so that C bonded to O is visible near G l u superscript 276, which projects from a long chain from which H I s superscript 274 projects above. Part c is similar but shows oseltamivir within the pocket. Oseltamivir has a chain with carbons but no oxygens near G l u superscript 276, which is bent up instead of down. Part d is similar to part c except that H i s has been replaced by T y r superscript 274, which has an oxygen that projects down near the former location of G l u superscript 276 (shown as a dotted illustration). G l u superscript 276 has moved slightly lower.

Some of the most devastating of the human parasitic diseases, widespread in much of the developing world, are caused by eukaryotic microorganisms that display unusual surface oligosaccharides, which in some cases are known to be protective for the parasites. These organisms include the trypanosomes, responsible for African sleeping sickness (see Box 6-1) and Chagas disease; Plasmodium falciparum, the malaria parasite; and Entamoeba histolytica, the causative agent of amoebic dysentery. The prospect of finding drugs that interfere with the synthesis of these unusual oligosaccharide chains, and therefore with the replication of the parasites, has inspired much recent work on the biosynthetic pathways of these oligosaccharides.

Lectins also act intracellularly, in sorting proteins for transportation to specific cellular compartments (see Chapter 27). For example, an oligosaccharide containing mannose 6-phosphate, recognized by a lectin, acts as a molecular “ZIP code” that tags newly synthesized proteins in the Golgi complex for transfer to the lysosome (see Fig. 27-41).

Lectin-Carbohydrate Interactions Are Highly Specific and Often Multivalent

The high density of information in the structure of oligosaccharides provides a sugar code with an essentially unlimited number of unique “words” small enough to be read by a single protein. In their carbohydrate-binding sites, lectins have a subtle molecular complementarity that allows interaction only with their correct carbohydrate binding partners. Often a divalent metal ion such as ${Ca}^{2 +}$ $Ca Superscript 2 plus$ or ${Mn}^{2 +}$ $Mn Superscript 2 plus$ is part of the binding site. Lectin-ligand interactions can have extraordinarily high specificity. The affinity between an oligosaccharide and an individual carbohydrate binding domain (CBD) of a lectin is sometimes modest (micromolar to millimolar $K_{d}$ $upper K Subscript d$ values), but the effective affinity is often greatly increased by lectin multivalency, in which a single lectin molecule has multiple CBDs. In a cluster of oligosaccharides — as is commonly found on a membrane surface, for example — each oligosaccharide can engage one of the lectin’s CBDs, strengthening the interaction. When cells express multiple lectin receptors, the avidity of the interaction can be very high, enabling highly cooperative events such as cell attachment and rolling (Fig. 7-29).

X-ray crystallographic studies of the structure of the lectin that is the receptor for mannose 6-phosphate reveal details that explain the specificity of the binding and the role of a divalent cation in the lectin-sugar interaction (Fig. 7-31). When the protein tagged with mannose 6-phosphate reaches the lysosome (which has a lower internal pH than the Golgi complex), the receptor loses its affinity for mannose 6-phosphate and the tagged protein is released into the lysosomal matrix.

A two-part figure, a and b, shows a lectin-carbohydrate interaction. — FIGURE 7-31 Details of a lectin-carbohydrate interaction. (a) Structure of the bovine mannose 6-phosphate receptor complexed with mannose 6-phosphate. The protein is represented as a surface contour image, showing the surface as predominantly negatively charged (red) or positively charged (blue). Mannose 6-phosphate is shown as a space-filling model; a manganese ion is shown as a violet sphere. (b) An enlarged view of the binding site. Mannose 6-phosphate is hydrogen-bonded to $mathml alt text1$ $Arg Superscript 111$ and coordinated with the manganese ion (shown smaller than its van der Waals radius, for clarity). Each hydroxyl group of mannose is hydrogen-bonded to the protein. The $mathml alt text1$ $Arg Superscript 105$ hydrogen-bonded to a phosphate oxygen of mannose 6-phosphate may be the residue that, when protonated at low pH, causes the receptor to release mannose 6-phosphate into the lysosome. [Data from PDB ID 1M6P, D. L. Roberts et al., *Cell* 93:639, 1998.]

FIGURE 7-31 Details of a lectin-carbohydrate interaction. (a) Structure of the bovine mannose 6-phosphate receptor complexed with mannose 6-phosphate. The protein is represented as a surface contour image, showing the surface as predominantly negatively charged (red) or positively charged (blue). Mannose 6-phosphate is shown as a space-filling model; a manganese ion is shown as a violet sphere. (b) An enlarged view of the binding site. Mannose 6-phosphate is hydrogen-bonded to $mathml alt text1$ $Arg Superscript 111$ and coordinated with the manganese ion (shown smaller than its van der Waals radius, for clarity). Each hydroxyl group of mannose is hydrogen-bonded to the protein. The $mathml alt text1$ $Arg Superscript 105$ hydrogen-bonded to a phosphate oxygen of mannose 6-phosphate may be the residue that, when protonated at low pH, causes the receptor to release mannose 6-phosphate into the lysosome. [Data from PDB ID 1M6P, D. L. Roberts et al., *Cell* 93:639, 1998.]

Part a shows a bumpy, irregular molecule with a red region to the lower left, a blue region above and in the middle, and white elsewhere. A space-filling molecule of black and red atoms is visible in the middle with a single orange atom on the left side. Additional molecules are visible as ball-and-stick models all around it. Part b shows the molecules inside without the overall bumpy, irregular structure. The central molecule is shown as a ball-and-stick model. It has a ring to the right with a carbon chain extending to a red atom bonded to the orange atom on the left, which has red atoms on the three free sides. H i s superscript 105 is shown above with a black dotted line from a blue segment of its ring to the top red atom and with a dotted black line from a blue segment on its chain to a red atom bonded to the orange atom from the rear left. A s n superscript 104 runs vertically to the left and has a dotted black line from a blue segment to the red atom bonded to the orange atom from the rear left. A s p superscript 103 is below and has a dotted black line from a blue segment to the front red atom bonded to the orange atom. A large purple atom labeled M n has a dotted black line to the front red atom bonded to the orange atom. Dotted black lines also extend from M n to a red segment in A s p superscript 103 and to a small red segment below and to the left. M n also has a dotted black line to a blue segment at the top of an A r g superscript 111 in the middle of the image, beneath the ball-and-stick model. Two sets of vertical blue lines extend from blue parts on A r g superscript 111 to a red atom below the ring of the main ball-and-stick model. To the right, G l n superscript 66 is in the lower right corner and has a dotted black line from a blue segment to the same red atom extending down from the ring of the ball-and-stick ring model that has hydrogen bonds (vertical blue lines) to A r g superscript 111. T y r superscript 143 is adjacent and just above to G l n superscript 66. T y r superscript 45 is slightly higher in the center of the right side and has two sets of vertical blue lines representing hydrogen bonds from the red part above its ring to two red atoms on the ring of the ball-and-stick model. G l u superscript 133 is just behind T y r superscript 45 and runs up behind the ring of the ball-and-stick model. A r g superscript 135 is at the top of the illustration and has three horizontal blue lines connecting it to a red atom in the ring of the ball-and-stick model.

In addition to such highly specific interactions, there are more general interactions that contribute to the binding of many carbohydrates to their lectins. For example, many sugars have a more polar side and a less polar side (Fig. 7-32); the more polar side hydrogen-bonds with the lectin, while the less polar side undergoes interactions with nonpolar amino acid residues through the hydrophobic effect. The sum of all these interactions produces high-affinity binding and high specificity of lectins for their carbohydrate ligands. This represents a kind of information transfer that is clearly central in many processes within and between cells. Figure 7-33 summarizes some of the biological interactions mediated by the sugar code.

A figure shows how the hydrophobic effect contributes to interactions of sugar residues. — FIGURE 7-32 Interactions of sugar residues due to the hydrophobic effect. Sugar units such as galactose have a more polar side (the top of the chair as shown here, with the ring oxygen and several hydroxyls), available to hydrogen-bond with the lectin, and a less polar side that can interact with nonpolar side chains in the protein, such as the indole ring of Trp residues, through the hydrophobic effect. [Information from a figure provided by Dr. C.-W. von der Lieth, Heidelberg; H.-J. Gabius, *Naturwissenschaften* 87:108, 2000, Fig. 6.]

A part of a large, indistinct shaded surface is shown, featuring a large invagination from the left that contains several molecules. At the bottom, a six-membered ring is joined by its bottom side to a five-membered ring that has a bond extending from its bottom vertex to the edge of the shaded surface. It is labeled indolyl moiety of T r p. Above it, there is a chair form of a six-membered ring with C 1 extended down and C 4 extended upward. O is between C 5 and C 1 and has two sets of blue lines between it and the edges of the shaded surface. C 1 is bonded to O H at an angle above the ring and H vertically below the ring; C 2 is bonded to H vertically above the ring and to O H at an angle below the ring; C 3 is bonded to O H at an angle above the ring and H vertically below the ring; C 4 is bonded to O vertically above the ring and to H at an angle below the ring; C 5 is bonded to C 6 above the ring and to H vertically below the ring. The O H bonded to C 4 has two sets of blue lines between O and the boundary of the shaded surface and an additional set of blue lines between H at the boundary of the shaded surface. Text near the boundary of the invagination above the ring reads hydrophilic side. Text in the interior of the invagination, to the left of the ring, reads hydrophobic side.

A figure shows the role of oligosaccharides in recognition events at the cell surface and in the endomembrane system. — FIGURE 7-33 Role of oligosaccharides in recognition events at the cell surface and in the endomembrane system. (a) Oligosaccharides with unique structures (represented as strings of red hexagons) are components of a variety of glycoproteins or glycolipids on the outer surface of plasma membranes. Their oligosaccharide moieties are bound by extracellular lectins with high specificity and affinity. (b) Viruses that infect animal cells, such as the influenza virus, bind to cell surface glycoproteins as the first step in infection. (c) Bacterial toxins, such as the cholera and pertussis toxins, bind to a surface glycolipid before entering a cell. (d) Some bacteria adhere to and then colonize or infect animal cells. (e) Selectins (lectins) in the plasma membrane of certain cells mediate cell-cell interactions, such as those of leukocytes with the endothelial cells of the capillary wall at an infection site. (f) The mannose 6-phosphate receptor/lectin of the trans Golgi complex binds to the oligosaccharide of lysosomal enzymes, targeting them for transfer into the lysosome. [Information from N. Sharon and H. Lis, *Sci. Am.* 268 (January):82, 1993.]

A figure shows a curved cell membrane with the interior of the cell below. Parts of the figure are labeled from a to f. Part a shows a helical plasma membrane protein running across the plasma membrane with a thread-shaped piece extending into the cell below and a similar thread extending above. There is an oligosaccharide chain attached near the end of the thread outside of the cell. The chain has six hexagons with a branch of three hexagons extending from the third hexagon to the end. A glycolipid is shown to the left as a green sphere in line with the phosphate heads on the outer surface of the membrane with two green tails extending down. There is a chain of four hexagons extending up from it with an additional hexagon extending to the right of the second hexagon from the top. Part b shows a similar protein to part a with an oligosaccharide chain, but the chain is surrounded by an opening in a large structure that is wide at the bottom and narrow at the top, where it extends into a circle labeled virus. Part c shows a glycolipid like the one described previously except that an irregular oval structure labeled toxin is above it with a cutout in the bottom surrounding the oligosaccharide chain. Part d shows a protein with an oligosaccharide chain similar to the one in part b, except that it extends into a circle labeled bacterium instead of a circle labeled virus. Part e shows the membrane of a leukocyte as a portion of a second cell membrane with a protein embedded into it which ends with an oligosaccharide chain extending down, where it fits into a circular cutout in a large molecule labeled P selectin that narrows as it passes through the first cell membrane and then widens into a sphere within the main cell below. Part f, within the main cell, shows a curved piece of membrane labeled trans Golgi with an oval labeled enzyme inside. An oligosaccharide chain extending from the enzyme is labeled mannose 6-phosphate residue on newly synthesized protein and fits into a cutout in the rounded bottom side of a large molecule that becomes thinner as it passes through the trans Golgi membrane and emerges on the other side, where it is labeled mannose 6-phosphate receptor / lectin. An arrow points from this structure to a circular membrane labeled lysosome that contains a similar enzyme that also has a mannose 6-phosphate residue on newly synthesized protein extending into a mannose 6-phosphate receptor / lectin that extends across the membrane to the outside of the lysosome.

SUMMARY 7.4 Carbohydrates as Informational Molecules: The Sugar Code

Monosaccharides can be assembled into an almost limitless variety of oligosaccharides, which differ in the stereochemistry and position of glycosidic bonds, the type and orientation of substituent groups, and the number and type of branches. Glycans are far more information-dense than nucleic acids or proteins.
The sugar specificity of many plant lectins makes them powerful laboratory reagents in glycobiology. Receptor/lectins in the surface of hepatocytes recognize glycoproteins that have lost their terminal sialic acid residue and mediate the normal uptake (by hepatocytes) and destruction of blood cells and of certain circulating glycoprotein hormones.
Bacterial and viral pathogens and some eukaryotic parasites adhere to their animal cell targets through binding of lectins on the pathogens to oligosaccharides on the target cell surface, or vice versa. Interactions are often polyvalent.
Structural studies of lectin-sugar complexes show the detailed complementarity between the two molecules, which accounts for the strength and specificity of lectin interactions with carbohydrates.