Biochemical Engineering Fundamentals, Part 1 - Bailey J., Ollis D. 1989

The Chemical Basis of Life
Mixed-Structure Biochemical Compounds
Antibodies and Other Glycoproteins

Proteins containing covalently bound monosaccharide residues or short oligosaccharide chains are called Glycoproteins. A wide variety of glycoproteins have been found in eukaryotes and their extracellular environment. These include several Enzymes, such as glucose oxidase produced by Aspergillus niger. The previously mentioned Collagen—a biological structural element—is also a glycosylated protein. Certain interferons, which are potent antiviral agents, are also glycoproteins. In fact, most eukaryotic proteins that interact with the cellular environment or are secreted into it are glycoproteins. Some glycoproteins have already become, or are highly likely to soon become, valuable industrial products. The Biosynthesis of glycoproteins and their role in transport processes will be discussed in Chapters 5 and 6.

Antibodies, which are the primary weapon of the vertebrate immune defense system, are also glycoproteins (Fig. 2.26). Using the Cell Fusion Methods discussed in Chapter 6, homogeneous antibodies can be produced in large quantities in animal systems or bioreactors. This will enable the widespread future use of antibodies for diagnostic purposes, drug delivery, and the Separation of biologically important substances. For this reason, it seems appropriate to briefly discuss the origin, Structure, and function of antibodies here.

The vertebrate immune system includes B Cells, which belong to one of the two MAIN TYPES OF lymphocytes found in the body. In the presence of a foreign substance, virus, or cell (an antigen), B cells differentiate into plasma cells that secrete antibodies. These antibodies specifically bind Antigens (and structurally related substances); the resulting antigen-antibody complex precipitates and is cleared from the body.

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FIG. 2.26. a—Schematic diagram of immunoglobulin structure. The symbols C and V denote the constant and variable Regions of the chains, respectively, while the subscripts H and L denote the heavy and light chains, respectively. Disulfide Bonds are shown, as well as the attachment site of the carbohydrate moiety (CHO) to the heavy chains. The stem region (F_c) and the antigen-binding site are located at the carboxyl and amine terminals of the heavy chains, respectively. Antigen-binding Specificity and affinity are determined by the variable regions of both heavy and light chains; b—Molecular STRUCTURE OF THE IgG antibody, immunoglobulin G. [Reproduced with permission from Silverton E. W., Navia M. A., Davies D. R., Proc. Natl. Acad. Sci., 74, 5142 (1977).]

Antibodies belong to a specific class of proteins called IMMUNOGLOBULINS; the General Structural Features characteristic of immunoglobulins are shown in Fig. 2.26. An immunoglobulin molecule consists of two identical, longer 'heavy' chains linked to each other by disulfide bonds, and non-covalently linked to two other, also identical, but shorter 'light' chains. In the most common class of immunoglobulins, designated IgG, the light and heavy chains have molecular weights of 23,000 and 53,000, respectively. The C-terminal regions of both light and heavy chains, which are virtually identical in structure within the same class of immunoglobulins, are called constant regions. The F_c region, which forms the stem of the antibody molecule, is composed of the C-terminal sequences of the HEAVY CHAIN CONSTANT regions.

Antibody variation within a single class is primarily determined by the N-terminal regions of the chains, known as variable regions. The antigen-binding site of the antibody (paratope) is formed by the variable regions of both light and heavy chains. Similar to the catalytic activity of enzymes, the antigen-binding sites in different antibodies can vary significantly in their specificity and affinity for antigens.