Immunoglobulin domain structure

Figure 33.7. Immunoglobulin Sequence Diversity. A plot of sequence variability as a function of position along the sequence of the amino-terminal immunglobulin domain of the H chain of human IgG molecules. Three regions (in red) show remarkably high levels of variability. These hypervariable regions correspond to three loops in the immunoglobulin domain structure. [After R. A. Goldsby, T. J. Kindt, and B. A. Osborne, Kuby Immunology, 4th ed. (W. H. Freeman and Company, 2000), p. 91.]...

All immunoglobulin domains have similar three-dimensional structures... 

Many other cell-surface proteins involved in immunological recognition utilize immunoglobulin-like domains as structural elements. Immunoglobulin domains have been classified into five types, namely V (like antibody variable... 

Adhesion proteins in this group contain an immunoglobulin domain that is composed of 90-100 amino acids arranged in a sandwich of two sheets of antiparallei strands. Some members of this family also contain fibronectin type III—like domains in addition to the immunoglobulin domain. Immunoglobulin-related adhesion proteins either can exist as transmembrane structures or can be attached to cell membranes via glycosyl phosphatidylinositol links (B4, R5). 

However, only the extracellular domains immediately adjacent to the cell membrane and the (32 microglobulin peptide have clear homology with the immunoglobulin domains. The al and ct2 segments of class I and the al and (31 domains in class II have quite an unusual structure. Class I molecules are present on virtually every cell in the body, the most notable exception being the syncytial trophoblast of the placenta. Class II expression is far more restricted B cells, dendritic cells which present antigen to T cells, and macrophage express abundant class II molecule on their surfaces. However, most other tissues can be induced to express class II molecules under the influence of soluble mediators such as 7-interferon. 

Fig. 2. Examples of the structures of protein domains and repeats. The images were generated using Molscript (Kraulis, 1991). (A) Immunoglobulin domain (PDB identifier ltlk) (Holden et al1992), (B) A zinc finger domain with coordinated zinc ion (PDB identifienlzaa) (Pavletich and Pabo, 1991). (C) A /3-propeller domain composed of seven WD40 repeats (PDB identifier lgp2) (Wall et al., 1995), (D) An elongated domain of variant leucine-rich repeats (PDB identifienllrv) (Peters et al., 1996).

Erickson HP. Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. Proc Natl Acad Sci USA 1994 91 10114-10118. 

An IgG molecule consists of a total of 12 immunoglobulin domains. These domains have many sequence features in common and adopt a common structure, the immunoglobulin fold (Figure 33,9). Remarkably, this same structural domain is found in many other proteins that play key roles in the immune system. 

Figure 33.9. Immunoglobulin Fold. An immunoglobulin domain consists of a pair of P-sheets linked by a disulfide bond and hydrophobic interactions. Three hypervariable loops lie at one end of the structure.

Figure 33.33. Class II MHC Protein. A class IIMHC protein consists of homologous a and P chains, each of which has an amino-terminal domain that constitutes half of the peptide-binding structure, as well as a carboxyl-terminal immunoglobulin domain. The peptide-binding site is similar to that in class I MHC proteins except that it is open at both ends, allowing class II MHC proteins to bind longer peptides than those bound by class I.

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