Amino acid sequence of the first constant region domain and the hinge region of the delta heavy chain of human IgD.

Abstract

BiochemistryAmino acid sequence of the first constant region domain and the hinge region of the 6 heavy chain of human IgD ( ABSTRACT We have determined the amino acid sequence of the first constant (C) region domain (C61) and the hinge region of the 6 heavy chain of human IgD WAH and also the sequence of the adjacent COOH-terminal portion of the variable (V) region, including the JH region. Together with the sequence ofthe Fc fragment already reported, this establishes the complete amino acid sequence of the C region of the human 8 chain and confirms the presence of three C region domains in human IgD. Although the CH1 domains of the five classes of human heavy chains have the expected degree of homology (='30%), the homology of the C,61 domains of the human and mouse chains is less than that exhibited by the CHI domains of other pairs of human and mouse heavy chains. The hinge region of the human 6 chain has an unusual structure; the NH2-terminal half has four (or five) GalN oligosaccharides attached, whereas the COOH-terminal half lacks carbohydrate, is dissimilar in sequence, and has a high charge. A computer search verified that the GalN-rich segment has a high degree of identity in sequence with the middle portion of the human C02 domain and that the high-charge segment is related to the same sequence. We propose that the two segments of the human 5 hinge have a common evolutionary origin and arose by duplication and independent mutation of a hinge exon derived from the ancestral gene for the C ,A2 domain.

Complete amino acid sequence of the delta heavy chain of human immunoglobulin D.

“…Peptides were prepared by digestion with trypsin, chymotrypsin, or Staphylococcus aureus V8 protease (2,3). The aminoterminal CNBr fragment of the 8 chain was resistant to these enzymes and so was digested with pepsin and also cleaved by iodosobenzoic acid or dilute acid (0.03 M HCl).…”

“…However, mounting evidence that this minor class ofcirculating immunoglobulins has a major function as an antigen receptor on the membrane of B lymphocytes (10,11) led us to undertake determination of the complete primary structure of human IgD. We have reported the complete amino acid sequence of the Fc region (2) and of the C81 and hinge regions (3), which together constitute the entire constant (C) region ofthe 8 chain of the myeloma protein WAH. Here, we report the structure ofthe variable (V) region ofthe heavy (H) chain (the VH region), which completes the amino acid sequence of the 8 H chain; in work to be reported separately, we have determined the entire sequence ofthe A light (L) chain, which completes the structure of a human IgD molecule.…”

“…Although sequence data have been published for more than 50,000 amino acid residues of immunoglobulins of various classes and species, until recently (1)(2)(3)(4)(5)(6)(7)(8) little was known about the amino acid sequence of human IgD. The reasons include: (i) the low concentration of serum IgD except in rare patients with multiple myeloma, (ii) the apparent lack of a characteristic antibody activity or effector function, (iii) the extreme sensitivity of IgD to "spontaneous" proteolytic degradation (1,9), and (iv) the unusual structure of the hinge region, which presented difficult technical problems for its determination (5,6).…”

Duck immunoglobulins: Structure, functions and molecular genetics

“…The heavy chains of IgD, IgA and the IgGs all have three C H domains and a hinge region that joins the Fab regions to the Fc. Putnam et al, (1980) have suggested that the hinge region exon evolved by mutation of the C H 2 domain-encoding exon, and Parvari et al (1988) pointed out that the COOH-terminal residues (cysteineproline) of the chicken C H 2 domain can be found at the COOH ends of many mammalian hinge regions. Recent modelling studies of Padlan (personal communication) have placed the hinge region of the IgE heavy chain at the C H 2 /C H 3 domain boundary; the IgE C H 2 /Cm interdomain has parallel disulphide bonds at its boundaries and shows considerable segmental flexibility, believed to be important in the effector processes arising from the interaction between the molecule and Fc e receptors (Helm et al, 1991).…”

Complete covalent structure of a human immunoglobulin D: sequence of the lambda light chain.

“…(iii) JA is more closely related to JH than it is to JK. EXPERIMENTAL PROCEDURES To determine the complete amino acid sequence of the A L chain we used the methods of automated sequence analysis described for the 6 chain (9,(15)(16)(17)(18). These were combined with a strategy based on the power of HPLC (high-performance liquid chromatography) to purify large peptides.…”