Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1969 Nov;64(3):997–1003. doi: 10.1073/pnas.64.3.997

SUBGROUPS OF AMINO ACID SEQUENCES IN THE VARIABLE REGIONS OF IMMUNOGLOBULIN HEAVY CHAINS*

Bruce A Cunningham 1, Mollie N Pflumm 1, Urs Rutisha User 1, Gerald M Edelman 1
PMCID: PMC223334  PMID: 5264153

Abstract

The amino acid sequence of the first 133 residues of the heavy (γ) chain from a human γG immunoglobulin (He) has been determined. This γ-chain is identical in Gm type to that of protein Eu, the complete sequence of which has been reported. Comparison of the two sequences substantiates the previous suggestion that there are subgroups of variable regions of heavy chains. The variable region of Eu has been assigned to subgroup I and that of He to subgroup II; on the other hand, the constant regions of the two proteins appear to be identical. Comparison of the sequence of the heavy chain of He with the heavy chain sequences determined in other laboratories suggests that the variable region of subgroup II is at least 118 residues long. The nature and distribution of amino acid variations in this heavy chain subgroup resemble those observed in light chain subgroups.

These studies provide evidence that the translocation hypothesis applies to heavy as well as to light chains, viz., genes for variable regions (V) are somatically translocated to genes for constant regions (C) to form complete VC structural genes.

Full text

PDF
997

Images in this article

1000Image
on p.1000
1001Image
on p.1001

Selected References

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

  1. Cummingham B. A., Gottlieb P. D., Konigsberg W. H., Edelman G. M. The covalent structure of a human gamma G-immunoglobulin. V. Partial amino acid sequence of the light chain. Biochemistry. 1968 May;7(5):1983–1994. doi: 10.1021/bi00845a049. [DOI] [PubMed] [Google Scholar]
  2. Dreyer W. J., Bennett J. C. The molecular basis of antibody formation: a paradox. Proc Natl Acad Sci U S A. 1965 Sep;54(3):864–869. doi: 10.1073/pnas.54.3.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Edelman G. M., Cunningham B. A., Gall W. E., Gottlieb P. D., Rutishauser U., Waxdal M. J. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci U S A. 1969 May;63(1):78–85. doi: 10.1073/pnas.63.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Edelman G. M., Gall W. E., Waxdal M. J., Konigsberg W. H. The covalent structure of a human gamma G-immunoglobulin. I. Isolation and characterization of the whole molecule, the polypeptide chains, and the tryptic fragments. Biochemistry. 1968 May;7(5):1950–1958. doi: 10.1021/bi00845a045. [DOI] [PubMed] [Google Scholar]
  6. FEINSTEIN A. CHARACTER AND ALLOTYPY OF AN IMMUNE GLOBULIN IN RABBIT COLOSTRUM. Nature. 1963 Sep 21;199:1197–1199. doi: 10.1038/1991197b0. [DOI] [PubMed] [Google Scholar]
  7. Gottlieb P. D., Cunningham B. A., Waxdal M. J., Konigsberg W. H., Edelman G. M. Variable regions of heavy and light polypeptide chains of the same gammaG-immunoglobulin molecule. Proc Natl Acad Sci U S A. 1968 Sep;61(1):168–175. doi: 10.1073/pnas.61.1.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hilschmann N., Craig L. C. Amino acid sequence studies with Bence-Jones proteins. Proc Natl Acad Sci U S A. 1965 Jun;53(6):1403–1409. doi: 10.1073/pnas.53.6.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hood L., Ein D. Immunologlobulin lambda chain structure: two genes, one polypeptide chain. Nature. 1968 Nov 23;220(5169):764–767. doi: 10.1038/220764a0. [DOI] [PubMed] [Google Scholar]
  10. Milstein C. Linked groups of residues in immunoglobulin k chains. Nature. 1967 Oct 28;216(5113):330–332. doi: 10.1038/216330a0. [DOI] [PubMed] [Google Scholar]
  11. Offord R. E. Electrophoretic mobilities of peptides on paper and their use in the determination of amide groups. Nature. 1966 Aug 6;211(5049):591–593. doi: 10.1038/211591a0. [DOI] [PubMed] [Google Scholar]
  12. Piggot P. J., Press E. M. Cyanogen bromide cleavage and partial sequence of the heavy chain of a pathological immunoglobulin G. Biochem J. 1967 Aug;104(2):616–626. doi: 10.1042/bj1040616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rutishauser U., Cunningham B. A., Bennett C., Konigsberg W. H., Edelman G. M. Amino acid sequence of the Fc region of a human gamma G-immunoglobulin. Proc Natl Acad Sci U S A. 1968 Dec;61(4):1414–1421. doi: 10.1073/pnas.61.4.1414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. SCHWARTZ J. H., EDELMAN G. M. Comparisons of Bence-Jones proteins and L polypeptide chains of myeloma globulins after hydrolysis with trypsin. J Exp Med. 1963 Jul;118:41–53. doi: 10.1084/jem.118.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. TODD C. W. Allotypy in rabbit 19S protein. Biochem Biophys Res Commun. 1963 May 3;11:170–175. doi: 10.1016/0006-291x(63)90329-2. [DOI] [PubMed] [Google Scholar]
  16. Waxdal M. J., Konigsberg W. H., Henley W. L., Edelman G. M. The covalent structure of a human gamma G-immunoglobulin. II. Isolation and characterization of the cyanogen bromide fragments. Biochemistry. 1968 May;7(5):1959–1966. doi: 10.1021/bi00845a046. [DOI] [PubMed] [Google Scholar]
  17. Wikler M., Köhler H., Shinoda T., Putnam F. W. Macroglobulin structure: homology of mu and gamma heavy chains of human immunoglobulins. Science. 1969 Jan 3;163(3862):75–78. doi: 10.1126/science.163.3862.75. [DOI] [PubMed] [Google Scholar]
  18. Wilkinson J. M., Press E. M., Porter R. R. The N-terminal sequence of the heavy chain of rabbit immunoglobulin IgG. Biochem J. 1966 Aug;100(2):303–308. doi: 10.1042/bj1000303. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES