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. 

Fig. 13.7. The rearrangement of a variable sequence by gene conversion. The top line shows a variable light chain comprising three CDRs and three framework regions (FR). Below are shown four rearrangments of this sequence in which pseudogenes have replaced different sections of the original sequence (Mastellar Thompson, 1994).

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). 

Figure 15.12 Schematic diagram of the barrel arrangement of four p strands from each of the variable domains in Fab. The six hypervariable regions, CDR1-CDR3 from the light chain (L1-L3) and from the heavy chain (H1-H3), are at one end of this barrel. (From J. Novotny et al., /. Biol. Chem. 2S8 14433-14437, 1983.)...

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. 

The constant domain has a stable framework structure composed of two antiparallel sheets comprising seven p strands, four in one sheet and three in the other. The variable domains have a similar framework structure but comprising nine p strands, five in one sheet and four in the other. The three hypervariable regions are in loops at one end of the variable domain. The variable domains from the heavy and light chains associate through their five-stranded p sheets to form a barrel with the hypervariable loop regions from both domains close together at the top of the barrel. 

Of the several kinase activities which are important in smooth muscle, myosin light chain kinase, MLCK, is the one responsible for activation of the actin-myosin system to in vivo levels. MLCK is present in the other nonmuscle cell types which have the actin-myosin contractile system and all of these are probably activated in a manner similar to smooth muscle rather than by way of the Ca -troponin mechanism of striated muscle. MLCK from smooth muscle is about 130 kDa and is rather variable in shape. It is present in smooth muscle in 1-4 pM concentrations and binds with an equally high affinity to both myosin and actin. Thus, most MLCK molecules are bound to actin. Myosin light chain serine-19 is the primary target of smooth muscle myosin light chain kinase. 

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. 

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