Heavy 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 plasminogen molecule contains several sites that specifically bind a number of antifibrinolytic amino acids, such as lysine [56-87-1] and S-aminocaproic acid [60-32-2] (EACA). These sites are known as lysine binding sites (LBS), and are localized mainly to the A or heavy chain of the molecule. One is located in K4 and at least one more is in K1 through K3. One LBS, which is beheved to reside in Kl, has a stronger affinity for EACA, whereas the others have a weaker affinity. The LBS are important for the interaction of plasminogen with several components of the endogenous fibrinolytic system. 

Figure 14.14 Sci ematic diagram of the myosin molecule, comprising two heavy chains (green) that form a coiled-coil tail with two globular heads and four light chains (gray) of two slightly differing sizes, each one bound to each heavy-chain globular head.

Figure 14.15 Stmcture of the SI fragment of chicken myosin as a Richardson diagram (a) and a space-filling model (b). The two light chains are shown in magenta and yellow. The heavy chain is colored according to three proteolytic fragments produced by trypsin a 25-kDa N-terminal domain (green) a central 50-kDa fragment (red) divided by a cleft into a 50K upper and a 50K lower domain and a 20-kDa C-terminal domain (blue) that links the myosin head to the coiled-coil tail. The 50-kDa and 20-kDa domains both bind actin, while the 25-kDa domain binds ATP. [(b) Courtesy of 1. Rayment.]...

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 15.2b). Each class of heavy chains can combine with either of the two different classes of light chains. 

In this chapter we will discuss immunoglobulins of the IgG class, which is the major type of immunoglobulin in normal human serum, and which has the simplest structure. Each chain of an IgG molecule is divided into domains of about 110 amino acid residues. The light chains have two such domains, and the heavy chains have four. 

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.)...

Figure 15.14 Schematic representation of the specific interactions between phosphoryicholine (orange) and the protein side groups (green) in Fab. The binding cavity is in a cleft between the light and the heavy chains. Choiine binds in the interior while the phosphate group is toward the surface. (Adapted from E.A. Padlan et al., Immunochemistry 13 945-949, 1976.)...

The CDR loops assume only a limited range of conformations, except for the heavy chain CDR3... 

The genes for MHC molecules, unlike immunoglobulin genes, do not undergo rearrangements to create structural diversity. The Pzm light chain is invariant, but the class I MHC heavy chain is the most genetically polymorphic... 

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. 

Figure 17.2 An example of prediction of the conformations of three CDR regions of a monoclonal antibody (top row) compared with the unrefined x-ray structure (bottom row). LI and L2 are CDR regions of the light chain, and HI is from the heavy chain. The amino acid sequences of the loop regions were modeled by comparison with the sequences of loop regions selected from a database of known antibody structures. The three-dimensional structure of two of the loop regions, LI and L2, were in good agreement with the preliminary x-ray structure, whereas HI was not. However, during later refinement of the x-ray structure errors were found in the conformations of HI, and in the refined x-ray structure this loop was found to agree with the predicted conformations. In fact, all six loop conformations were correctly predicted in this case. (From C. Chothia et al.. Science 233 755-758, 1986.)...

The cytosolic dyneins bear many similarities to axonemal dynein. The protein isolated from C. elegans includes a heavy chain with a molecular mass of approximately 400 kD, as well as smaller peptides with molecular mass ranging from 53 kD to 74 kD. The protein possesses a microtubule-activated ATPase... 

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