Fig. 4.1 Structure of an antibody molecule. in panel a, the X-ray crystallographic structure of an igg antibody is illustrated as a ribbon diagram of the backbones of the polypeptide chains. The two heavy chains are shown in yellow and purple. The two light chains are both shown in red. Three globular regions form an approximate Y shape. The two antigen-binding sites are at the tips of the arms, which are tethered at their other end to the trunk of the Y by a flexible hinge region. The light-chain variable (VL) and constant region (cL) are indicated. The heavy-chain variable region (Vh) and VL together form the antigen-binding site of the antibody. in panel b, a schematic representation of the same structure denotes each immunoglobulin domain as a separate rectangle. The hinge that tethers each heavy chain’s first constant domain (ch1) to its second (ch2) is illustrated by a thin purple or yellow line, respectively. The antibody-binding sites are indicated by concave regions in VL and Vh. Positions of carbohydrate modifications and disulfide linkages are indicated. in panel c, a more simplified schematic is shown that will be used throughout this book with the variable region in red and the constant region in blue. c terminus, carboxy terminus; n terminus, amino terminus. Structure courtesy of R.L. Stanfield and i.A. Wilson.
and to cells that destroy the antigen. Each of these tasks is performed by different parts of the molecule. The ends of the two arms of the Y—the V regions—are involved in antigen binding, and they vary in their detailed structure between different antibody molecules. The stem of the Y—the C region—is far less variable and is the part that interacts with effector molecules and cells. There are five different classes of immunoglobulins, distinguished in their being constructed from C regions that have different structures and properties. These are known as immunoglobulin M (IgM), immunoglobulin D (IgD), immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE).
All antibodies are constructed in the same way from paired heavy and light polypeptide chains, and the generic term immunoglobulin is used for all such proteins. More subtle differences confined to the V region account for the specificity of antigen binding. We will use the IgG antibody molecule as an example to describe the general structural features of immunoglobulins.
4-1 IgG antibodies consist of four polypeptide chains.
IgG antibodies are large molecules with a molecular weight of approximately 150 kDa and are composed of two different kinds of polypeptide chains. One, of approximately 50 kDa, is called the heavy or H chain, and the other, of 25 kDa, is the light or L chain (Fig. 4.2). Each IgG molecule consists of two heavy chains and two light chains. The two heavy chains are linked to each other by disulfide bonds, and each heavy chain is linked to a light chain by a disulfide bond. In any given immunoglobulin molecule, the two heavy chains and the two light chains are identical, giving an antibody molecule two identical antigen-binding sites. This gives the antibody the ability to bind simultaneously to two identical antigens on a surface, thereby increasing the total strength of the interaction, which is called its avidity. The strength of the interaction between a single antigen-binding site and its antigen is called its affinity.