Flexibility of immunoglobulins

The flexibility was more restricted in the nurse shark IgM. The above results, together with a steady-state fluorescence depolarization study on the flexibility of immunoglobulins from amphibia and reptiles has suggested that the degree of flexibility decreases with the level of phytogeny. Thus, time-resolved fluorescence depolarization measurements may provide one of the first techniques capable of indicating... 

A study of the time-resolved depolarization of the fluorracence from a dansyl (XIII) conjugate of an IgA myeloma protein revealed no internal flexibility i I. Comparison of these results with those for IgG, however, is not realistic since each of the several classes of immunoglobuline possess characteristic stmctural and biolc cal properties. 

S. Mukherjee, S.P. Pondaven, C.P. Jaroniec, Conformational flexibility of a human immunoglobulin light chain variable domain by relaxation dispersion nuclear magnetic resonance spectroscopy imphcations for protein misfolding and amyloid assembly. Biochemistry 50 (2011) 5845-5857. 

Holowka D, Wensel T, Baird B. A nanosecond fluorescence depolarization study on the segmental flexibility of receptor-bound immunoglobulin E. Biochemistry 1990 29 4607-4612. 

IgG antibody molecules are composed of two light chains and two heavy chains joined together by disulfide bonds. Each light chain has one variable domain and one constant domain, while each heavy chain has one variable and three constant domains. All of the domains have a similar three-dimensional structure known as the immunoglobulin fold. The Fc stem of the molecule is formed by constant domains from each of the heavy chains, while two Fab arms are formed by constant and variable domains from both heavy and light chains. The hinge region between the stem and the arms is flexible and allows the arms to move relative to each other and to the stem. 

The basic structure of an immunoglobulin molecule, such as the major serum antibody IgG, consists of four polypeptide chains two identical light chains (molecular weight around 25 000 daltons) and two identical heavy chains (with a molecular weight around 50 000 daltons), cross-linked by disulfide bonds to form Y-shaped molecules with two flexible arms (Fig. 11.2). The binding sites are located on the arms and vary from one molecule to another (variable region) [22b]. 

Even greater flexibility was achieved by genetic fusion of streptavidin with protein A [153,154]. Protein A specifically binds the Fc domain of IgG immunoglobulins of almost all mammals without inhibiting the antigen binding activity of the antibody. The streptavidin-protein A fusion construct was used for the assembly of complexes of biotinylated P-galactosidase and different monoclonal antibodies specific for tumour cell receptors. As a result these complexes were efficiently delivered into several cancer cell lines [154]. 

Electron microscopy of IgM and IgG reveals that the four-chain units in both immunoglobulins are shaped like a Y or T with a flexible central hinge (Green 1969). In IgM, the five Y-shaped tetramers form a ring with five arms projecting from it. 

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