Light chains disulfide bonds

Fig. 4.12. Amino acid sequences and sites of enzymatic cleavage in the hinge regions of human and rabbit-y chains. The symbol H represents the site of an interheavy chain disulfide bond and the symbol L designates the site of a heavy-light chain disulfide bond. The halfcystine at position 220 of the rabbit y-chain forms an intrachain disulfide loop with Cys 131 or 132. The Eu numbering system is used (2). Pap, Pep, and T refer to cleavage sites for papain, pepsin, and trypsin, respectively. The site of cleavage of the rabbit H chain by papain is that for molecules of allotype dll. Hydrolysis by papain of molecules of allotype dl2 is described in the text. Cleavage of the rabbit H chain by trypsin at position 220 occurs only after reduction and aminoethylation (by ethyleneimine) of Cys-220. The symbol CHO represents carbohydrate. References are given in the legend of Fig. 4.9.

Heavy chain -Disulfide bond Light chain —... 

Fig. 4. Simple model of an IgG molecule showing light- and heavy-chain segments where a line ( ) between the chains represents a disulfide bond. General Methodology.

The basic structure of all immunoglobulin (Ig) molecules comprises two identical light chains and two identical heavy chains linked together by disulfide bonds (Figure IS.2a). There are two different classes, or isotypes, of light chains, X and k, but there is no known functional distinction between them. Heavy chains, by contrast, have five different isotypes that divide the immunoglobulins into different functional classes IgG, IgM, IgA, IgD, and IgE, each with different effector properties in the elimination of antigen... 

Figure 15.17 The three-dimensional structure of an intact IgG. Hinge regions connecting the Fab arms with the Fc stem are relatively flexible, despite the presence of disulfide bonds in this region linking the heavy and light chains. Carbohydrate residues that bridge the two Ch2 domains are not shown. (Courtesy of A. McPherson and L. Harris, Nature 360 369-372, 1992, by copyright permission of Macmillan Magazines Limited.)...

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. 

Clostridial neurotoxins are bacterial protein toxins that consist of a heavy and a light chain connected by a disulfide bond and non-covalent interactions. They... 

Figure 6.2 The trifunctional reagent sulfo-SBED reacts with amine-containing bait proteins via its NHS ester side chain. Subsequent interaction with a protein sample and exposure to UV light can cause crosslink formation with a second interacting protein. The biotin portion provides purification or labeling capability using avidin or streptavidin reagents. The disulfide bond on the NHS ester arm provides cleavability using disulfide reductants, which effectively transfers the biotin label to an unknown interacting protein.

Fig. 3. Refolding model of insulin protofilaments, from Jimenez et al. (2002). (A) Ribbon diagram of the crystal structure of porcine insulin (PDB ID code 3INS), generated with Pymol (DeLano, 2002). The two chains are shown as dark and light gray with N- and C-termini indicated. The dotted lines represent the three disulfide bonds 1 is the intrachain and 2 and 3 are the interchain bonds. (B) Cartoon representation of the structure of monomeric insulin in the fibril, as proposed by Jimenez et al. (2002). The thick, arrowed lines represent /1-strands, and thinner lines show the remaining sequence. The disulfide bonds are as represented in panel A, and N- and C-termini are indicated. (Components of this panel are not to scale.) (C) Cartoon representation of an insulin protofilament, showing a monomer inside. The monomers are proposed to stack with a slight twist to form two continuous /(-sheets. (Components of this panel, including the protofilament twist, are not to scale.) In the fibril cross sections presented byjimenez et al. (2002), two, four, or six protofilaments are proposed to associate to form the amyloid-like fibrils.

The structure of an antibody is normally depicted as a capital letter Y configuration. IgG is the most predominant antibody. It is a tetrameric molecule consisting of two identical heavy (H) polypeptide chains of about 440 amino acids and two identical light (L) polypeptide chains of about 220 amino acids (Fig. 4.1).The four chains are held together by disulfide bonds and noncovalent interactions. 

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]. 

BoNTs (150 kDa) consist of two polypeptide chains the heavy chain (HC, 100 kDa) and the light chain (LC, 50 kDa), linked with disulfide and non-covalent bonds. The amine end of the LC is responsible for intraneural enzymatic activity. The HC contains a membrane translocation domain (a 50 kDa amino-terminal polypeptide) and a receptor-binding part (a 50 kDa carboxy-terminal polypeptide) (DasGupta, 1990 Krieglstein et ah, 1994). BoNT/A forms dimers, trimers, and bigger structures. BoNT/E generally has a monomer structure, but sometimes forms dimers. BoNT/B is a dimer (Ledoux et ah, 1994). 

Botulinum toxin is a mixture of six large molecules, each of which consists of two components. The two components, a heavy (100 kDa) and light (50 kDa) polypeptide chain, are connected via a disulfide bond. The toxin may be associated with and protected from stomach acid by proteins such as hemogglutinins, which dissociate in the more alkaline intestine. 

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