Repetitive hinge region sequences in human IgG3: isolation of an 11,000-dalton fragment.
The heavy chain (gamma-3) of the IgG3 subclass of human immunoglobulins has a molecular weight of 60,000, instead of the 50,000 value reported for gamma-1, gamma-2, and gamma-4 heavy chains. By use of protein Omm, a gamma-3 heavy chain disease protein, it was possible to isolate and analyze the extra fragment. Protein Omm had a molecular weight of 40,000, glycine as its sole NH-2-terminal, and contained only the hingee region and the C-H-2 and C-H-3 domains. CNBr cleavage at Met 252 (gamma-1 numbering) yielded the hinge fraction (Fh fragment). On the basis of the molecular weight of Fh (11,000), its amino-acid composition, its partial sequence, and its unexpectedly low number of tryptic peptides, it is postulated that the extra fragment in gamma-3 heavy chains represents a series of similar or identical duplications of sections of the previously reported gamma-3 hinge region. In addition, there are striking homologies with the hinge region of alpha-1 and alpha-2 heavy chains, one of which also has duplications. The relationship of these hinge structures in different immunoglobulins supports the concept that this region is coded by a unique, small piece of DNA, which has evolved in parallel manner with the immunogolbulin genes by partial duplications and/or crossingover.
D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D003488:Cyanogen Bromide; D004586:Electrophoresis; D006801:Humans; D006868:Hydrolysis; D007128:Immunoglobulin Fragments / Q000032:analysis* / Q000302:isolation & purification*; D007074:Immunoglobulin G / Q000032:analysis*; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*; D008970:Molecular Weight; D009194:Myeloma Proteins / Q000032:analysis; D014357:Trypsin
D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D009194:Myeloma Proteins; D014357:Trypsin; D003488:Cyanogen Bromide