Immunoglobulin variable-light chain

Structures of TNF-K antagonists used in rheumatoid arthritis. CH, constant heavy chain CL, constant light chain Fc, complex immunoglobulin region VH, variable heavy chain VL, variable light chain. Red regions, human derived blue regions, mouse derived. 

Malcolm, S., Barton, P., Murphy, C., Ferguson-Smith, M.A., Bentley, D.L., Rabbits, T.H. (1982). Localization of human immunoglobulin K light chain variable region genes to the short arm of chromosome 2 by in situ hybridization. Proc. Natl. Acad. Sci. USA 79,4957-4961. 

Sanchez, P., Marche, P.N., Le Guem, C., Cazenave, P.-A. (1987). Structure of a third murine immunoglobulin X light chain variable region that is expressed in laboratory mice. Proc. Natl. Acad. Sci. USA 84,9185-9188. 

Taub, R.A., Hollis, G.F., Hieter, P.A., Korsmeyer, S., Waldmann, T.A., Leder, P. (1983). Variable amplification of immunoglobulin X light-chain genes in human populations. Nature 304,172-174. 

The most remarkable feature of the antibody molecule is revealed by comparing the amino acid sequences from many different immunoglobulin IgG molecules. This comparison shows that between different IgGs the amino-terminal domain of each polypeptide chain is highly variable, whereas the remaining domains have constant sequences. A light chain is thus built up from one amino-terminal variable domain (Vl) and one carboxy-terminal constant domain (Cl), and a heavy chain from one amino-terminal variable domain (Vh), followed by three constant domains (Chi, Ch2. and Chs). 

IgG antibody molecules are composed of two light chains and two heavy chains joined together by disulfide bonds. Each light chain has one variable domain and one constant domain, while each heavy chain has one variable and three constant domains. All of the domains have a similar three-dimensional structure known as the immunoglobulin fold. The Fc stem of the molecule is formed by constant domains from each of the heavy chains, while two Fab arms are formed by constant and variable domains from both heavy and light chains. The hinge region between the stem and the arms is flexible and allows the arms to move relative to each other and to the stem. 

Each immunoglobulin light chain is the product of at least three separate strucmral genes a variable region... 

Stevens PW, Raffen R, Hanson DK, Deng YL, Berrios Hammond M, Westholm FA, Murphy C, Eulitz M, Wetzel R, Solomon A, et al. Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins. Protein Sci 1995 4 421-432. 

Shirahama, T., Benson, M. D., Cohen, A. S., and Tanaka, A. (1973). Fibrillar assemblage of variable segments of immunoglobulin light chains An electron microscopic study. / Immunol. 110, 21-30. 

Figure 1.10. Generalised structure of the variable and constant domains within antibodies. The variable regions (dark shading) of either the light or heavy chains are indicated as VL or VH, respectively. The light chains also possess one constant region (CL), whereas the heavy chains possess either three or four constant regions (Ch)-Ch4). depending upon the class of immunoglobulin (see text for details).

The basic structure of an immunoglobulin molecule, such as the major serum antibody IgG, consists of four polypeptide chains two identical light chains (molecular weight around 25 000 daltons) and two identical heavy chains (with a molecular weight around 50 000 daltons), cross-linked by disulfide bonds to form Y-shaped molecules with two flexible arms (Fig. 11.2). The binding sites are located on the arms and vary from one molecule to another (variable region) [22b]. 

It is estimated that more than 10 different antibody variants occur in every human being. This variability affects both the heavy and the light chains of immunoglobulins. 

Human clone 7E3 immunoglobulin Light chain variable region (VkJ)... 

GI 13785651 Light chain immunoglobulin G2 variable region [synthetic construct] ... 

The fundamental structure of immunoglobulins was first established by Gerald Edelman and Rodney Porter. Each chain is made up of identifiable domains some are constant in sequence and structure from one IgG to the next, others are variable. The constant domains have a characteristic structure known as the immunoglobulin fold, a well-conserved structural motif in the all /3 class of proteins (Chapter 4). There are three of these constant domains in each heavy chain and one in each light chain. The heavy and light chains also have one variable domain each, in which most of the variability in amino acid residue sequence is found. The variable domains associate to create the antigen-binding site (Fig. 5-24). 

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