Immunoglobulin structure

Homologous proteins have similar three-dimensional structures. They contain a core region, a scaffold of secondary structure elements, where the folds of the polypeptide chains are very similar. Loop regions that connect the building blocks of the scaffolds can vary considerably both in length and in structure. From a database of known immunoglobulin structures it has, nevertheless, been possible to predict successfully the conformation of hyper-variable loop regions of antibodies of known amino acid sequence. 

The immunoglobulin structure in Figure 6.45 represents the confluence of all the details of protein structure that have been thus far discussed. As for all proteins, the primary structure determines other aspects of structure. There are numerous elements of secondary structure, including /3-sheets and tight turns. The tertiary structure consists of 12 distinct domains, and the protein adopts a heterotetrameric quaternary structure. To make matters more interesting, both intrasubunit and intersubunit disulfide linkages act to stabilize the discrete domains and to stabilize the tetramer itself. 

The enzymes commonly used as labels in ELISA and other immunochemical reactions include horse radish peroxidase (HRP) and alkaline phosphatase (AP). The enzyme can be covalently coupled to the antibody using glutaraldehyde conjugation to reactive amino groups on the enzyme (lysines) in a phosphate buffered aqueous solution at neutral pH, as shown in Fig. 19 (103). Alternatively, carbohydrates present in the immunoglobulin structure can be cleaved by periodate treatment (see Fig. 20) and bound to free amino groups on the enzyme through a Schiff base reaction (103). 

Extensive reviews have been written on the structure of immunoglobulins (Ig s).4,5 For understanding of the present article, a brief description of immunoglobulin structure is essential. 

Immunoglobulins of classes IgGl, IgG2, IgA, and IgM are measurable in milk. IgG has the familiar immunoglobulin structure, with two heavy and two light chains. IgA is found in milk as a dimer of two IgA complexes, linked by one J and one SC chain. Negative IgM is a pentamer of IgM complexes attached to one J chain (Walstra and Jenness 1984). 

Structural domains of proteins are sometimes encoded by a single coding segment of DNA i.e., by a single exon in a split gene. Domains of this type may have served as evolutionarily mobile modules that have spread to new proteins and multiplied during evolution. For example, the immunoglobulin structural domain is found not only in antibodies but also in a variety of cell surface proteins.229 252... 

It may be worthwhile to recall that many quite different proteins are members of the immunoglobulin structural family (Fig. 2-16). These include proteins... 

Now we demonstrate how to examine the mutability of specified residues in a protein. Two positions in an immunoglobulin structure are compared with respect to the number of stabilizing mutations among all possible substitutions. A singlesite mutability profile is generated for two regions of the structure, pointing to sites that may be more important for structural stability than others. 

The final session demonstrates how to characterize a protein region as random-izable. For a set of solvent-exposed residues of an immunoglobulin structure, 103 mutants are randomly generated. We examine how many of these mutants are destabilized with respect to the wild type. The analysis is repeated with an alternative set of residues that correspond to part of the natural epitope of the immunoglobulin structure. 

Here, the situation is almost reversed only a minority of the mutants (1.1%) exhibit a combined z-score that indicates destabilization (Figure 11.9 and 11.10 for a comparison of the z-score distributions). This result is in good agreement with our prior knowledge about immunoglobulin structures the amino acids of the epitope are supposed to be primarily selected for binding the antigen, rather than for their contribution to structural stability. 

Carayannopoulos L, Capra JD. 1993. Immunoglobulins Structure and function. In Paul WE, Ed. Fundamental Immunology. 3rd Ed., Raven Press, New York. 

Wang, A.-C., Wang, I.Y., Fudenberg, H.H. (1977). Immunoglobulin structure and genetics. Identity between variable regions of a p and a y2 chain. J. Biol. Chem. 252,7192-7199. 

Five classes of Humans have five different classes of antibody molecule which differ both in immunoglobulins structure and in function. These are called immunoglobulin A (IgA), IgD, IgE, IgG and IgM and each has its own type of heavy chain a, 8, e, y and x, respectively. Thus IgA molecules have two identical a heavy chains, IgD molecules have two identical 8 heavy chains, etc. The human IgG class of antibodies is further divided into four IgG subclasses IgG, IgG2, IgG3 and IgG4, having y, y2, y3 and y4 heavy chains respectively. 

Figure 8-2. Schematic representation of polypeptide chains in the basic immunoglobulin structure. [From D. R. Davies, E. A. Padlan, and D. M. Segal, Ann. Rev. Biochem., 44 639 (1975). ...

Fig. 1. Immunoglobulin structure. (IgF occurs transiently in the fetus and has not yet been found after birth.) Reproduced by courtesy of the British Medical Journal (H35).

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