Tomotaka Shinoda

Complete amino acid sequence of the Mu heavy chain of a human IgM immunoglobulin

The amino acid sequence of the �, chain of a human IgM immunoglobulin, including the location of all disulfide bridges and oligosaccharides, has been determined. The homology of the constant regions of immunoglobulin �, γ, α, and ε heavy chains reveals evolutionary relationships and suggests that two genes code for each heavy chain.

Macroglobulin Structure: Homology of Mu and Gamma Heavy Chains of Human Immunoglobulins

The amino acid sequence of fragments obtained by cyanogen bromide cleavage of the mu-chain of a human γM-globulin is homologous to the NH2-terminal sequences of the gamma-chain of human and rabbit γG-globulins and is related to that of human light chains. This supports the hypothesis that light and heavy chains evolved from a common ancestral gene.

Immunoglobulin Structure: Variation in Amino Acid Sequence and Length of Human Lambda Light Chains

Variation and conservation in the primary structure of human lambda light chains is revealed by complete amino acid sequence of three Bence Jones proteins. These proteins differ in amino acid sequence in from 38 to 48 positions; they are of unequal length in the amino-terminal half of the chain but have identical sequence in the last 105 amino acids.

Variation and Homology in the Mu and Gamma Heavy Chains of Human Immunoglobulins

Sequence analysis of an 1gM immunoglobulin shows that the variable regions of hunman � and γ1 heavy chainis may have twice as much homology as their constant regions and that evolutionary divergence of � and γ1 heavy chain genes occurred not long after the separation of heavy and light chain genes.

The amino acid sequence of human macroglobulins.

Due to the importance of IgM immunoglobulin as the predominant antibody in the newborn animal and in the primary immune response, as well as its role in various autoimmune diseases, we have undertaken to determine the complete amino acid sequence of a human IgM macroglobulin with a covalent molecular weight approximating one million. This protein (Ou) from a patient with macroglobulinemia serves as a model for structural study of IgM antibodies, just as Bence-Jones proteins have for light chains and myeloma globulins have for IgG immunog1obulins.l Structural study of such proteins has shown that antibodies are composed of a pair of heavy and a pair of light polypeptide chains disulfide-bonded together to form a tetrachain immunoglobulin molecule with two specific combining sites (FIGURE 1) . In the three major classes of immunoglobulins IgG, IgM, and IgA (or yG, yM, and yA), the heavy chains are y, p , and a, respectively, and the light chains may be either K or A. IgM is unique in having a pentameric structure with a sedimentation coefficient of 19s (corrected value); even higher polymers of about 29s and 38s may be present in small amounts. Because of the myriad possible number of antigens that exist, a capacity for great variability is required for the structure of the antibody combining site. Amino acid sequence analysis of pathological proteins has shown that this is provided for by a variable-sequence region of some 110-120 amino acid residues at the NH, terminus of each chain. Both the heavy and the light chains are divided into regions of variable and constant sequence. The variable (V) regions of the heavy and light chains differ in sequence and together determine the structure of the combining site. The constant (C) regions determine the class of the chain and certain associated biological properties. Whereas both the variable and constant regions of light chains are characteristic of the light chain type (i.e., are either both K or X),3 the class character of heavy chains is not expressed in the variable region (V,) but only in the constant region (CH). Thus, a comparison 4, of the NH,-terminal region of several p, y, and (Y chains has indicated that four variable-sequence subgroups are common to heavy chains ( V H I V H I V ) . Although the complete amino acid sequence of the y chains of at least five human IgG myeloma globulins is now and much sequence information is available on the VH portions of y and p chains,4, lo only fragmentary portions of the sequence of the C,, region of p chains are published.,. Comparative sequence data on human p and y chains would be of great value for testing the hypothesis that immunoglobulins evolved by gene duplication after early divergence of V and

Tentative Structure of Human IgM Immunoglobulin

Publisher Summary This chapter discusses the structure of human IgM immunoglobulin. Human IgM immunoglobulin has a pentameric structure in which each monomeric unit consists of a pair of μ heavy chains and a pair of light chains linked by disulfide bonds. Each heavy chain has four interchain disulfide bonds. Two bonds are located between the pair of μ chains in the monomer, one to the light chain, and one bond forms the intersubunit bridge between the monomers. The κ light chains and the μ heavy chains are each divided into a variable region at the NH2 terminus and a constant region. The variable regions of the L and H chains are almost the same length (about 110 to 120 residues, respectively). The constant region of the μ heavy chain is about four times as long as the constant region of the κ light chain to which it is joined. Trypsin at 60° cleaves the IgM pentamer into monomeric Fabμ fragments and a decameric Fcμ portion of the heavy chain. Tryptic cleavage occurs in the hinge region just prior to the first μ–μ interchain disulfide bridge.