• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Feb 1975; 72(2): 723–727.
PMCID: PMC432388

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Edelman GM, Cunningham BA, Gall WE, Gottlieb PD, Rutishauser U, Waxdal MJ. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci U S A. 1969 May;63(1):78–85. [PMC free article] [PubMed]
  • Frangione B, Milstein C, Pink JR. Structural studies of immunoglobulin G. Nature. 1969 Jan 11;221(5176):145–148. [PubMed]
  • Frangione B, Milstein C, Franklin EC. Chemical typing of immunoglobulins. Nature. 1969 Jan 11;221(5176):149–151. [PubMed]
  • Frangione B, Milstein C. Partial deletion in the heavy chain disease protein ZUC. Nature. 1969 Nov 8;224(5219):597–599. [PubMed]
  • Saluk PH, Clem LW. The unique molecular weight of the heavy chain from human IgG3. J Immunol. 1971 Jul;107(1):298–301. [PubMed]
  • Turner MW, Bennich HH, Natvig JB. Pepsin digestion of human G-myeloma proteins of different subclasses. I. The characteristic features of pepsin cleavage as a function of time. Clin Exp Immunol. 1970 Nov;7(5):603–625. [PMC free article] [PubMed]
  • Michaelsen TE, Natvig JB. The hinge region of IgG3, an extended part of the molecule. FEBS Lett. 1972 Nov 15;28(1):121–124. [PubMed]
  • Frangione B, Wolfenstein-Todel C. Partial duplication in the "hinge" region of IgA 1 myeloma proteins. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3673–3676. [PMC free article] [PubMed]
  • SCHEIDEGGER JJ. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed]
  • OUCHTERLONY O. Antigen-antibody reactions in gels. IV. Types of reactions in coordinated systems of diffusion. Acta Pathol Microbiol Scand. 1953;32(2):230–240. [PubMed]
  • Weber K, Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed]
  • Andrews P. The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem J. 1965 Sep;96(3):595–606. [PMC free article] [PubMed]
  • Woods KR, Wang KT. Separation of dansyl-amino acids by polyamide layer chromatography. Biochim Biophys Acta. 1967 Feb 21;133(2):369–370. [PubMed]
  • Frangione B, Milstein C. Variations in the S-S bridges of immunoglobins G: interchain disulfide bridges of gamma G3 myeloma proteins. J Mol Biol. 1968 May 14;33(3):893–906. [PubMed]
  • Brown JR, Hartley BS. Location of disulphide bridges by diagonal paper electrophoresis. The disulphide bridges of bovine chymotrypsinogen A. Biochem J. 1966 Oct;101(1):214–228. [PMC free article] [PubMed]
  • Frangione B, Milstein C, Franklin EC. Intrachain disulphide bridges in immunoglobulin G heavy chains. The Fc fragment. Biochem J. 1968 Jan;106(1):15–21. [PMC free article] [PubMed]
  • KATZ AM, DREYER WJ, ANFINSEN CB. Peptide separation by two-dimensional chromatography and electrophoresis. J Biol Chem. 1959 Nov;234:2897–2900. [PubMed]
  • Levin M, Franklin EC, Frangione B, Pras M. The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. J Clin Invest. 1972 Oct;51(10):2773–2776. [PMC free article] [PubMed]
  • Frangione B. A technique for the detection of deleted immunoglobulin heavy chains. Biochemistry. 1973 Aug 14;12(17):3355–3359. [PubMed]
  • Michaelsen TE, Natvig JB. Unusual molecular properties of human IgG3 proteins due to an extended hinge region. J Biol Chem. 1974 May 10;249(9):2778–2785. [PubMed]
  • Offord RE. Electrophoretic mobilities of peptides on paper and their use in the determination of amide groups. Nature. 1966 Aug 6;211(5049):591–593. [PubMed]
  • Watanabe S, Barnikol HU, Horn J, Bertram J, Hilschmann N. Die Primärstruktur eines monoklonalen IgM-Immunoglobulins (Makroglobulin Gal.), II. Die Aminosäuresequenz der H-Kette (mu-Typ,Subgruppe HIII), Struktur des gesamten IgM-Moleküls. Hoppe Seylers Z Physiol Chem. 1973 Oct-Nov;354(10-11):1505–1509. [PubMed]
  • Frangione B, Franklin EC. Heavy chain diseases: clinical features and molecular significance of the disordered immunoglobulin structure. Semin Hematol. 1973 Jan;10(1):53–64. [PubMed]
  • Michaelsen TE, Natvig JB, Sletten K. Isolation of a fragment, Fh, corresponding to the hinge region of human IgG3. Scand J Immunol. 1974;3(4):491–498. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...