Amino acid sequences immunoglobulins

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. 

The most remarkable feature of the antibody molecule is revealed by comparing the amino acid sequences from many different immunoglobulin IgG molecules. This comparison shows that between different IgGs the amino-terminal domain of each polypeptide chain is highly variable, whereas the remaining domains have constant sequences. A light chain is thus built up from one amino-terminal variable domain (Vl) and one carboxy-terminal constant domain (Cl), and a heavy chain from one amino-terminal variable domain (Vh), followed by three constant domains (Chi, Ch2. and Chs). 

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. 

Recombinant DNA technology has also facilitated detailed study of cytokine receptors. Based upon amino acid sequence homology, receptors are usually classified as belonging to one of six known superfamilies (Table 8.3). Individual members of any one superfamily characteristically display 20-50 per cent homology. Conserved amino acids normally occur in discrete bands or clusters, which usually correspond to a discrete domain in the receptor. Most receptors exhibit multiple domains. In some cases a single receptor may contain domains characteristic of two or more superfamilies. For example, the IL-6 receptor contains domains characteristic of both the haematopoietic and immunoglobulin superfamilies, making it a member of both. 

There are different classes and subclasses of immunoglobulins which are determined by the amino acid sequence of the light and heavy chains. 

In summary, for all the immunoglobulin molecules within one class, the amino acid sequence in the constant region of the chains is identical the massive number of different molecules within each class is accounted for by the amino acid sequences in the variable and hypervariable regions of both the light and heavy chains. 

Molecular studies over the years, including sequence analysis of immunoglobulins and their genes, revealed that amino-acid sequences in constant regions of the H chains found in Fc fragments are the same in individual subjects within the same species but different among species. The sequence differences between species are... 

While some of the immunoglobulins have been subjected to amino acid and carbohydrate analysis (Kumar and Mikalajcik 1973) and the amino acid sequence of certain portions of the heavy chains of IgGi and IgG2 have been investigated, the heterogeneity observed within each class of immunoglobulins makes the use of this knowledge in the... 

About 20% of milk protein is soluble in the aqueous phase of milk. These serum proteins are primarily a mixture of /3-lactoglobulin, a-lactalbumin, bovine serum albumin, and immunoglobulins. Each of these globular proteins has a unique set of characteristics as a result of its amino acid sequence (Swaisgood 1982). As a group, they are more heat sensitive and less calcium sensitive than caseins (Kinsella 1984). Some of these characteristics (Table 11.1) cause large differences in susceptibility to denaturation (de Wit and Klarenbeek 1984). 

Sequence determinations showed that in some regions of immunoglobulin molecules there is extreme variation in the amino acid sequence between one homogeneous antibody and the next other regions have a constant sequence. The molecule can also be divided into domains. The variable regions, which occupy the N-terminal ends of the chains, are designated... 

About 40% of human immunoglobulin light chains are X (Hood et al., 1967). Early studies of X chains produced by patients with multiple myeloma identified four types of C regions that were distinguished serologically and/or by amino acid sequence analysis they appeared not to be allelic and were presumed to be the products of distinct C genes (Appella and Ein, 1967 Ein and Fahey, 1967 Ein, 1968 Hess et al., 1971 Gibson et al., 1971 Fett and Deutsch, 1975). 

Appella, E. (1971). Amino acid sequences of two mouse immunoglobulin lambda chains. Proc. Natl. Acad. Sci. USA 68, 590-594. 

Burstein, Y. Schechter, I. (1977). Glutamine as a precursor to N-terminal pyrrolid-2-one-5-carboxylic acid in mouse immunoglobulin X-type light chains. Amino acid-sequence variability at the N-terminal extra piece of X-type light-chain precursors. Biochem. J. 165, 347-354. 

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