Epitome - Database of Structurally inferred Antigenic Epitopes in Proteins

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Antibodies, or immunoglobulines (Ig), are Y shaped proteins complexes composed of four polypeptide chains, two identical light chains and two identical heavy chains. Each light chain is bound to a heavy chain via disulfide bridges to form a heterodimer. Two identical heterodimers are linked to each other by disulfide bridges to form the basic antibody molecule (Fig. 1). The constant domains of the heavy chain (Fc) determine the biological function of the antibody creating five major classes of antibodies found in higher verterbrates (IgG, IgA, IgD, IgE and IgM). The variable domains (Fab), however, are involved in antigen binding. Within the Fab regions there are six hypervariable loops (3 on the surface of the light chain and 3 on the surface of the heavy chains) that directly interact with the antigen named the Complementarity Determining Regions (CDRs) (Fig. 2).

Fig 1. The basic structure of antibodies. Antibodies are Y shaped molecules. The heavy chains are colored in purple and green and the light chains are colored in pink and yellow. Fig 2. The Fab region and the Complementarity Determining Regions (CDRs) of an antibody - The Fab region of the antibody is composed of the antibody light chain (colored in white) and variable part of the heavy chain (in red). The 6 loops defining the CDRs according to Kabat identification scheme are colored grey (the heavy chain CDRs) and blue (the light chain CDRs).

Antigenic determinants, or epitopes, are particular surface areas of a protein that are specifically recognized by immunoglobulin molecules. Epitopes are commonly classified as either linear or conformational. Linear epitopes are continuous amino acid sequences of five to ten residues. When a protein is denatured or digested into several segments, peptides corresponding to the linear epitope amino acid sequences can sometimes be recognized by the antibody (Fig. 3a ). Conformational epitopes are however discontinuous and occur as a result of the higher order of the structure (Fig. 3b). After denaturation or digestion into small fragments, the peptides corresponding to the amino acid sequences of the conformational epitopes can no longer bind the antibody (some conformational epitopes were found to be composed of a number of linear epitopes).

Fig 3. Schematic representation of two antibodies interacting with linear and conformational epitopes.
a. Linear epitopes are short and continuous. After denaturation the linear epitopes may still be able to bind the antibody.

b. Conformational epitopes are domains of proteins composed of specific regions of protein chains. After denaturation the discontinuous epitope can no longer bind the antibody.

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