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. 1970 Mar;65(3):557–563. doi: 10.1073/pnas.65.3.557

Absence of Disulfide Bonds Linking the Heavy and Light Chains: A Property of a Genetic Variant of γA2 Globulins*

L M Jerry 1,2, H G Kunkel 1,2, H M Grey 1,2,†
PMCID: PMC282943  PMID: 5267137

Abstract

The γA2 globulins have attracted considerable interest because of the absence of the disulfide bonds linking the heavy and light chains characteristic of all other human immune globulins. Recently a genetic marker (Am2) has been found which delineates two genetic variants of γA2 globulins that are controlled by allelic genes. These differ markedly in incidence in different populations with a marked preponderance in Caucasians of the type possessing the Am2 marker. A study of 22 γA2 myeloma proteins primarily from Caucasians showed that 20 were Am2(+), and 2 were Am2(-). All of the positive type dissociated in the presence of acid or urea into heavy and light chain dimers without reduction of disulfide bonds, as expected from the earlier studies. However, the two Am2(-) proteins failed to dissociate in the presence of acid, urea, guanidine, or detergent. It was only after partial reduction and alkylation that these molecules split into heavy and light chains. Thus the unique absence of disulfide bonds linking the heavy and light chains is a property of only one genetic variant and not of all γA2 proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abel C. A., Grey H. M. Studies on the structure of mouse gamma-A myeloma proteins. Biochemistry. 1968 Jul;7(7):2682–2688. doi: 10.1021/bi00847a035. [DOI] [PubMed] [Google Scholar]
  2. Cohen S., Milstein C. Structure and biological properties of immunoglobulins. Adv Immunol. 1967;7:1–89. doi: 10.1016/s0065-2776(08)60126-1. [DOI] [PubMed] [Google Scholar]
  3. Edelman G. M., Gall W. E. The antibody problem. Annu Rev Biochem. 1969;38:415–466. doi: 10.1146/annurev.bi.38.070169.002215. [DOI] [PubMed] [Google Scholar]
  4. FLEISCHMAN J. B., PAIN R. H., PORTER R. R. Reduction of gamma-globulins. Arch Biochem Biophys. 1962 Sep;Suppl 1:174–180. [PubMed] [Google Scholar]
  5. Frangione B., Milstein C., Pink J. R. Structural studies of immunoglobulin G. Nature. 1969 Jan 11;221(5176):145–148. doi: 10.1038/221145a0. [DOI] [PubMed] [Google Scholar]
  6. Gold E. R., Fudenberg H. H. Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol. 1967 Nov;99(5):859–866. [PubMed] [Google Scholar]
  7. Grey H. M., Abel C. A., Yount W. J., Kunkel H. G. A subclass of human gamma-A-globulins (gamma-A2) which lacks the disulfied bonds linking heavy and light chains. J Exp Med. 1968 Dec 1;128(6):1223–1236. doi: 10.1084/jem.128.6.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HERZENBERG L. A. A CHROMOSOME REGION FOR GAMMA 2A AND BETA 2A GLOBULIN H CHAIN ISOANTIGENS IN THE MOUSE. Cold Spring Harb Symp Quant Biol. 1964;29:455–462. doi: 10.1101/sqb.1964.029.01.048. [DOI] [PubMed] [Google Scholar]
  9. Heimer R., Jones D. W., Maurer P. H. The immunoglobulins of sheep colostrum. Biochemistry. 1969 Oct;8(10):3937–3944. doi: 10.1021/bi00838a009. [DOI] [PubMed] [Google Scholar]
  10. Jordan E. M., Raymond S. Gel electrophoresis: a new catalyst for acid systems. Anal Biochem. 1969 Feb;27(2):205–211. doi: 10.1016/0003-2697(69)90024-4. [DOI] [PubMed] [Google Scholar]
  11. Kunkel H. G., Prendergast R. A. Subgroups of gamma-A immune globulins. Proc Soc Exp Biol Med. 1966 Jul;122(3):910–913. doi: 10.3181/00379727-122-31287. [DOI] [PubMed] [Google Scholar]
  12. Kunkel H. G., Smith W. K., Joslin F. G., Natvig J. B., Litwin S. D. Genetic marker of the gamma-A2 subgroup of gamma-A immunoglobulins. Nature. 1969 Sep 20;223(5212):1247–1248. doi: 10.1038/2231247a0. [DOI] [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  15. OLINS D. E., EDELMAN G. M. RECONSTITUTION OF 7S MOLECULES FROM L AND H POLYPEPTIDE CHAINS OF ANTIBODIES AND GAMMA-GLOBULINS. J Exp Med. 1964 May 1;119:789–815. doi: 10.1084/jem.119.5.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. PEACOCK A. C., BUNTING S. L., QUEEN K. G. SERUM PROTEIN ELECTROPHORESIS IN ACRYLAMIDE GEL: PATTERNS FROM NORMAL HUMAN SUBJECTS. Science. 1965 Mar 19;147(3664):1451–1453. doi: 10.1126/science.147.3664.1451. [DOI] [PubMed] [Google Scholar]
  17. Prahl J. W. The C-terminal sequences of the heavy chains of human immunoglobulin G myeloma proteins of differing isotopes and allotypes. Biochem J. 1967 Dec;105(3):1019–1028. doi: 10.1042/bj1051019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  19. Seki T., Appella E., Itano H. A. Chain models of 6.6S and 3.9S mouse myeloma gamma A immunoglobulin molecules. Proc Natl Acad Sci U S A. 1968 Nov;61(3):1071–1078. doi: 10.1073/pnas.61.3.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shapiro A. L., Viñuela E., Maizel J. V., Jr Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels. Biochem Biophys Res Commun. 1967 Sep 7;28(5):815–820. doi: 10.1016/0006-291x(67)90391-9. [DOI] [PubMed] [Google Scholar]
  21. Trautman R., Spragg S. P., Halsall H. B. Absorption optics data processing with standards errors for sedimentation and diffusion coefficients from moving boundary ultracentrifugation. Anal Biochem. 1969 Apr 4;28(1):396–415. doi: 10.1016/0003-2697(69)90195-x. [DOI] [PubMed] [Google Scholar]
  22. Vaerman J. P., Heremans J. F., Laurell C. B. Distribution of alpha-chain subclasses in normal and pathological IgA-globulins. Immunology. 1968 Mar;14(3):425–432. [PMC free article] [PubMed] [Google Scholar]
  23. Vaerman J. P., Heremans J. F. Subclasses of human immunoglobulin a based on differences in the alpha polypeptide chains. Science. 1966 Aug 5;153(3736):647–649. doi: 10.1126/science.153.3736.647. [DOI] [PubMed] [Google Scholar]
  24. 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] [Google Scholar]

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