Ch2 domain

Figure 15.17 The three-dimensional structure of an intact IgG. Hinge regions connecting the Fab arms with the Fc stem are relatively flexible, despite the presence of disulfide bonds in this region linking the heavy and light chains. Carbohydrate residues that bridge the two Ch2 domains are not shown. (Courtesy of A. McPherson and L. Harris, Nature 360 369-372, 1992, by copyright permission of Macmillan Magazines Limited.)...

Immunoglobulins contain carbohydrate moiety linked mainly to the CH2 domain of the Fc fragment, i. e., again far from the antigen binding sites. These sugar... 

CH1 barrels contact front-to-front and pairs of CH2 domains are quite widely separated by carbohydrate (Silverton et al., 1977). Of course, the great majority of homologous proteins have homologous subunit contacts, but it seems that even a quite drastic change in subunit contacts is easier to accommodate than major internal rearrangement. 

Immunoglobulins are glycoproteins. The carbohydrate moiety is attached to the heavy chain (usually the Ch2 domain) via an N-linked glycosidic bond. Removal of the carbohydrate group has no effect upon antigen binding but does affect various antibody effector functions and alters its serum half-life. 

Fig. 1. Structure of the antibody fusion protein. The Fab-like form is formed from a X light chain derived from the J558L cell line, and the chimenc heavy chain produced from the vector. The heavy chain consists of a variable region with NIP binding activity, CH1, hinge and part of the CH2 domain of murine y2b heavy chain, and the foreign gene. The fusion protein may be secreted in this form or as an F(ab )2-like form consisting of 2 Fab-like molecules linked at the hinge region by three disulfide bonds...

The fusion vector pSV-VNpY2bA(CH2, CH3) (1,5) is shown in Fig. 2. This plasmid is derived from pSV2gpt (6). It contains the variable region, VNP, the CH1, hinge, and the N-terminal part of the CH2 domain of the y2b heavy chain of a mouse antibody that binds to the haptens NP (4-hydroxy-3-mtrophene-cetyl) and NIP (5-iodo-4-hydroxy-3-nitrophenacetyl). 

Fig. 5 Summary of the different oriented IgG antibody immobilization methods a antibody is coupled to the solid support via an oxidized carbohydrate moiety in the CH2 domain of its Fc fragment b antibody binds to Fc receptors on solid supports c monovalent Fab fragment is bound to an insoluble support via a sulfhydryl group in the C-terminal region of the fragment...

Engineered IgG antibodies have been constructed with altered affinity to human Fey receptors and altered potency in vitro and in animal models [14, 31-33]. Mutations of critical residues in the Fc region (CH2 domain or the hinge region joining CH1 and CH2) have enhanced or decreased antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [33-37]. In addition, alterations in residues located at the CH2 domain of I gC, i involved in binding with Clq protein, a component of the complement activation cascade, resulted in a significant increase in CDC activity [34, 35]. 

Canfield SM, Morrison SL.The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. J Exp Med 1991 173(6) 1483-91. 

Etanercept is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kDa (p75) TNFR linked to the Fc portion of human IgGI. The Fc component of etanercept contains the CH2 domain, the CH3 domain, and hinge region, but not the CHi domain of igGI. It consists of 934 amino acids and has an apparent MW of approximateiy 150 kDa. 

N-linked carbohydrate moieties at Asn297 of the Ch2 domain and a protein A binding site between Ch2 and Ch3 [9, 10],... 

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