Immunoglobulins, structure and

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. 

Most of the known antiparallel p structures, including the immunoglobulins and a number of different enzymes, have barrels that comprise at least one Greek key motif. An example is 7 crystallin, which has two consecutive Greek key motifs in each of two barrel domains. These four motifs are homologous in terms of both their three-dimensional structure and amino acid sequence and are thus evolutionarily related. 

Segal, D.M., et al. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen-binding site. Proc. Natl. Acad. Sci. USA 71 4298-4302, 1974. 

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. 

A beta barrel is a three-dimensional protein fold motif in which beta strands connected by loops form a barrellike structure. For example, this fold motif is found in many proteins of the immunoglobulin family and of the chymotrypsin family of serine proteases. 

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