Hinge region of IgG

Sketch the polypeptide chains of an IgG molecule, and relate the heavy chain (H)-light chain (L) subunit composition (H2L2) to the and F, fragments of the molecule. Understand the function of the hinge region of IgG. 

A segment rich in proline, around residue 230, may possibly be homologous with the hinge region of IgG, but it lacks the interchain disulfide bonds characteristic of that region and shows no extra length of polypeptide in alignment with the other domains (Fig. 3.2). It is, however, one site of attack by trypsin (109). The complete sequence of the /A chain of protein Ou is presented in Chapter 4 (Fig. 4.10). 

Lengths of AMrNO Acid Sequences in Intrachain Disulfide Loops The Hinge Region of IgG... 

Figure 1.77 Disulfide reducing agents such as 2-mercaptoethylamine can be used to cleave the disulfide bonds in the hinge region of antibody molecules. Either intact IgG molecules or F(ab )2 fragments may be reduced in this manner to yield monofunctional antigen binding fragments.

Figure 20.4 Reduction of the disulfide bonds within the hinge region of an IgG molecule produces half-anti-body molecules containing thiol groups. Reaction of these reduced antibodies with a maleimide-activated enzyme creates a conjugate through thioether bond formation.

Fig. 4.— The General Appearance of IgG and IgA Molecules, Showing the Less Flexible Hinge-region of the IgA Molecule.

The single J chain in IgM (106) is disulfide bonded to the penultimate half-cystine residue of one, or possibly two /a chains (111,112). This would suggest an asymmetry in the IgM molecule, since a half-cystine linked to a J chain cannot also be part of an intrasubunit disulfide bond, and it is believed that most of the penultimate half-cystines do form such bonds this question requires further clarification. The L-H disulfide bonds in IgM involve half-cystine 140 in the H chain in this respect IgM is similar to molecules of the various subclasses of IgG, except for IgG 1 in which the L-H disulfide bond utilizes a half-cystine in the hinge region of the y chain. 

One recurring structural feature is the successive attachment of two residues of A -acetylglucosamine to an asparagine side chain these residues are followed by a mannose group to which two branches of the chain are attached. Sialic acid, when present, is at the end of a chain. A second major type of carbohydrate chain, found in IgM but not IgG, is rich in mannose (Fig. 4.20). So far only the first of the two types of chain structure has been identified in IgA both are present in IgE (137,138). An unusual carbohydrate structure, present in the hinge region of IgA, is discussed below in Section X,E. 

Figure 1.8b Amino acid sequence of the hinge region of different subclasses of human IgG. Solid lines indicate identity to yl chain. Shaded blocks indicate gaps to maximize homology. The sequence of y3 is taken from y3 HCD protein OMM, where it was postulated that the hinge region contains a series of similar or identical duplications (not shown). H and L indicate the position of interchain disulphide bonds. Established points of different between yl, 2, 3, and 4 are underlined.

---