(Also see color figure.) Schematic diagram of an immunoglobulin. (A) The simplest immunoglobulin (Ig) molecule, IgG consists of four polypeptide chains: two heavy chains
of ~50,000 Da and two light chains of ~25,000 Da. More complex Ig molecules are dimers or pentamers that consist of similar basic structures but may have slightly different
heavy and/or light chains. Each of the two heavy chains (shown in blue) contains four immunoglobulin domains, a variable VH domain at the N terminus, and three “constant”
domains, CHI, CH2, and CH3. Each of the light chains contains two domains, VL and CL. An immunoglobulin domain is 110-120 amino acids in length. The V domains of
both chains contain three regions described as hypervariable regions (orange bands) within the VH and VL domains. Each domain contains one intrachain disulfide bridge. The
CHI and the CL1 domains are linked by a single, interchain disulfide bridge. Two disulfide bridges join the two heavy chains near the N-terminal residues of the CH2 domain.
A single, Asn-linked, oligosaccharide chain is present within the CH2 domains of each of the heavy chains. A stretch of amino acids between the CHI and CH2 domains forms
a “hinge” region where the two heavy chains are connected by two disulfide bridges. The hinge region acts as a flexible tether between the CHI and CH2 domains. NMR
studies show this region to be very flexible, which permits the Ig molecule to assume various shapes, from the “Y” shown in the figure to a “T” with the “arms” perpendicular to
the Fc region (see below). The antigen-binding residues are located at the upper “tips” of the Y-shaped Ig molecule. In the folded Ig molecule, the residues of the hypervariable
regions are actually located at the tips, as can be seen in Figure 35-8. The portion of the IgG molecule above the dashed lines is the variable region; that portion below the
dashed lines is the constant region. (B) Immunoglobulin secondary structure. The secondary structures of all immunoglobulin domains are essentially the same. Each domain
contains seven antiparallel /3 sheets. The cystine residues (disulfide bonds) are space-filled in the figure. The open, accessible residues within the hinge are also evident in the
structure. The figure is derived from the coordinates published by E.A. Padlan,
M ol. Immunol.
169, 1994. (C) Space-filling model for IgG. Chains are color coded the same
throughout. The polypeptide regions comprising the hinge are readily accessible to proteolytic enzymes. Papain cleaves at the N-terminal side of the uppermost disulfide bridge
in the hinge to create three fragments; two Fab fragments containing the VH and CHI domains linked to the VL and CL domains by a single disulfide bond. The Fc fragment
contains two CH2 and two CH3 domains of the heavy chains.
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